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Background: Glioblastoma multiforme (GBM) is the vicious malignant brain tumor in adults. Despite advances multi-disciplinary treatment, GBM constinues to have a poor overall survival. CDDO-trifluoroethyl-amide (CDDO-TEFA), a trifluoroethylamidederivative of CDDO, is an Nrf2/ARE pathway activator. CDDO-TEFEA is used to inhibit proliferation and induce apoptosis in glioma cells. However, it not clear what effect it may have on tumorigenesis in GBM.Methods: This in vitro study evaluated the effects of CDDO-TFEA on GBM cells. To do this, we treated GBM8401 cell lines with CDDO-TFEA and assessed apoptosis, cell cycle. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis.Results: CDDO-TFEA significantly inhibited the cell viability and induced cell apoptosis on GBM 8401 cell line. The annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with CDDO-TFEA led to a significant reduction in the GBM8401 cells’ mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, treatment with CDDO-TFEA led to an accumulation of G2/M-phase cells. In addition, these results suggest that regarding increased protein synthesis during mitosis in the MPM-2 staining, indicative of a delay in the G2 checkpoint. An analysis of Cyclin B1, CDK1, Cyclin B1/CDK1 complex and CHK1 and CHK2 expression suggested that cell cycle progression seems also to be regulated by CDDO-TFEA. Therefore, CDDO-TFEA may not only induce cell cycle G2/M arrest, it may also exert apoptosis in established GBM cells.Conclusion: CDDO-TFEA can inhibit proliferation, cell cycle progression and induce apoptosis in GBM cells in vitro, possibly though its inhibition of Cyclin B1, CDK1 expression, and Cyclin B1/CDK1 association and the promotion of CHK1 and CHK2 expression.

Background: Malignant glioma (MG) is an aggressive malignant brain tumor. Despite advances in multidisciplinary treatment, overall survival rates remain low. A trifluoroethyl amide derivative of 2-cyano-3-,12-dioxoolean-1,9-dien-28-oic acid (CDDO), CDDO–trifluoroethyl amide (CDDO–TFEA) is a nuclear erythroid 2-related factor 2/antioxidant response element pathway activator. RTA404 is used to inhibit proliferation and induce apoptosis in cancer cells. However, its effect on tumorigenesis in glioma is unclear. Methods: This in vitro study evaluated the effects of RTA404 on MG cells. We treated U87MG cell lines with RTA404 and performed assessments of apoptosis and cell cycle distributions. DNA content and apoptosis induction were subjected to flow cytometry analysis. The mitotic index was assessed based on MPM-2 expression. Protein expression was analyzed through Western blotting. Results: RTA404 significantly inhibited the cell viability and induced cell apoptosis on the U87MG cell line. The Annexin-FITC/PI assay revealed significant changes in the percentage of apoptotic cells. Treatment with RTA404 led to a significant reduction in the U87MG cells’ mitochondrial membrane potential. A significant rise in the percentage of caspase-3 activity was detected in the treated cells. In addition, these results suggest that cells pass the G2 checkpoint without cell cycle arrest by RTA404 treatment in the MPM-2 staining. An analysis of CHK1, CHK2, and p-CHK2 expression suggested that the DNA damage checkpoint system seems also to be activated by RTA404 treatment in established U87MG cells. Therefore, RTA404 may not only activate the DNA damage checkpoint system, it may also exert apoptosis in established U87MG cells. Conclusions: RTA404 inhibits the cell viability of gliomas and induces cancer cell apoptosis through intrinsic apoptotic pathway in Malignant glioma. In addition, the DNA damage checkpoint system seems also to be activated by RTA404. Taken together, RTA404 activated the DNA damage checkpoint system and induced apoptosis through intrinsic apoptotic pathways in established U87MG cells.

Studies have identified the potential of chemopreventive effects of sulforaphane (SFN); however, the underlying mechanisms of its effect on breast cancer require further elucidation. This study investigated the anticancer effects of SFN that specifically induces G1/S arrest in breast ductal carcinoma (ZR-75-1) cells. The proliferation of the cancer cells after treatment with SFN was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA content and cell cycle status were analyzed through flow cytometry. Our results demonstrated the inhibition of growth in ZR-75-1 cells upon SFN exposure. In addition, SERTAD1 (SEI-1) caused the accumulation of SFN-treated G1/S-phase cells. The downregulation of SEI-1, cyclin D2, and histone deacetylase 3 suggested that in addition to the identified effects of SFN against breast cancer prevention, it may also exert antitumor activities in established breast cancer cells. In conclusion, SFN can inhibit growth of and induce cell cycle arrest in cancer cells, suggesting its potential role as an anticancer agent.

Cucurbitacin E (CuE), an active compound of the cucurbitacin family, possesses a variety of pharmacological functions and chemotherapy potential. Cucurbitacin E exhibits inhibitory effects in several types of cancer; however, its anticancer effects on brain cancer remain obscure and require further interpretation. In this study, efforts were initiated to inspect whether CuE can contribute to anti‐proliferation in human brain malignant glioma GBM 8401 cells and glioblastoma‐astrocytoma U‐87‐MG cells. An MTT assay measured CuE's inhibitory effect on the growth of glioblastomas (GBMs). A flow cytometry approach was used for the assessment of DNA content and cell cycle analysis. DNA damage 45β (GADD45β) gene expression and CDC2/cyclin‐B1 disassociation were investigated by quantitative real‐time PCR and Western blot analysis. Based on our results, CuE showed growth‐inhibiting effects on GBM 8401 and U‐87‐MG cells. Moreover, GADD45β caused the accumulation of CuE‐treated G2/M‐phase cells. The disassociation of the CDC2/cyclin‐B1 complex demonstrated the known effects of CuE against GBM 8401 and U‐87‐MG cancer cells. Additionally, CuE may also exert antitumour activities in established brain cancer cells. In conclusion, CuE inhibited cell proliferation and induced mitosis delay in cancer cells, suggesting its potential applicability as an antitumour agent.

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, for which radiotherapy and/or chemotherapy are the primary treatment methods. Many herbs are known to have potential uses in chemotherapy; however, the mechanisms underlying the observed antitumor activity of Ajuga bracteosa (AB) against NPC remain unclear. We explored the antitumor effects of AB, which was shown specifically to induce mitotic delay in pharyngeal (Detroit 562) and nasopharyngeal (Hone-1) cancer cells. Proliferation of cancer cells after exposure to aqueous extract of A. bracteosa (AEAB) was assessed using the MTT assay. DNA content and cell cycle arrest induction were analyzed using flow cytometry. The expression of checkpoint kinase 2 (CHK2), cell division control protein 2 (CDC2), and cyclin B1 was investigated using qRT-PCR and Western blot analysis. Results indicated the inhibition of cancer cell growth following exposure to AEAB. In addition, AEAB induced the accumulation of G2/M-phase cells in cancer cell through the disassociation of CDC2/cyclin B1 complex. Our findings suggested that, in addition to the known effects of AEAB in NPC prevention, it may have antitumor activities against NPC cells. In conclusion, AEAB inhibits the growth of and induces mitotic delay in cancer cells, supporting its use as an anticancer agent.

Cyclophosphamide is indicated for the treatment of cancerous diseases such as breast cancer and cervical cancer. Recent studies have shown that cyclophosphamide may induce cancer metastasis, but the cause of this unexpected adverse effect is not fully understood. In this study, we investigate the effect of cyclophosphamide on cancer cell migration and its correlation to chemokine (C-X-C motif) receptor 4 (CXCR4), a biomarker for cancer metastasis. Two human cancer cell lines with significant difference in endogenous CXCR4 expression, the breast cancer cell line, MDA-MB-231, and the melanoma cell line, MDA-MB-435S, were treated with various concentrations of cyclophosphamide, followed by the assessment of CXCR4 expression and cell migration. We found that the migration ability of MDA-MB-231 cells was enhanced with increasing concentrations of cyclophosphamide, which induced the cell-surface expression of CXCR4, but had no effect on the overall amount of CXCR4. In MDA-MB-435S cells, in which CXCR4 was barely detectable, cyclophosphamide was unable to activate cell-surface CXCR4, and did not promote cell migration. Studies on the mRNA expression profile of matrix metalloproteinases (MMPs) in MDA-MB-231 cells further indicate that MMP9 and MMP13 may be involved in the action of cyclophosphamide. The protein expression of both MMP9 and MMP13 was increased in the presence of cyclophosphamide. Results from this study provide the molecular basis for the possible pathway of cyclophosphamide to induce cancer metastasis.

The highest incidence of nasopharyngeal carcinoma (NPC) is in southeast China, including Taiwan. Many side effects have been observed following radiation therapy with chemotherapy; hence, exploring new treatment modalities for NPC is an important future direction. Angiotensin-(1–7) [Ang-(1–7)] is an endogenous heptapeptide hormone and important component of the renin–angiotensin system that acts through both the Mas receptor and AT2 receptor, exhibiting anti-proliferative and anti-angiogenic properties in cancer cells. However, the anti-cancer activity of Ang-(1–7) related to autophagy in NPC remains largely debated. The effects and signaling pathway(s) involved in the Ang-(1–7)/Mas receptor axis in NPC were investigated both in vitro and in vivo. Ang-(1–7) inhibited cell proliferation, migration, and invasion in NPC-TW01 cells. Ang-(1–7) induced autophagy by increasing the levels of the autophagy marker LC3-II and by enhancing p62 degradation via activation of the Beclin-1/Bcl-2 signaling pathway with involvement of the PI3K/Akt/mTOR and p38 pathways in vitro study. In addition, pre-treatment with Ang-(1–7) inhibited tumor growth in NPC xenografts by inducing autophagy, suggesting a correlation between PI3K/Akt/mTOR pathway inhibition and the abovementioned anti-cancer activities. However, no autophagy was observed following Ang-(1–7) post-treatment. Taken together, these data indicate that Ang-(1–7) plays a novel role in autophagy downstream signaling pathways in NPC, supporting its potential as a therapeutic agent for alleviation the incidence of NPC and preventive treatment of recurrent NPC. Key messages Ang-(1–7) inhibits cell proliferation, migration, and invasion by activating autophagyAng-(1–7)pre-treatment inhibits tumor growth via autophagy by suppressing PI3K/Akt/mTOR pathway.Ang-(1–7) may provide a novel preventative treatment for NPC and recurrent NPC Electronic supplementary material The online version of this article (10.1007/s00109-018-1704-z) contains supplementary material, which is available to authorized users.

Background. Severe burns result in hypercatabolic state and concomitant muscle atrophy that persists for several months, thereby limiting patient recovery. However, the effects of burns on the corresponding spinal dermatome remain unknown. This study aimed to investigate whether burns induce apoptosis of spinal cord ventral horn motor neurons (VHMNs) and consequently cause skeletal muscle wasting.Methods. Third-degree hindpaw burn injury with 1% total body surface area (TBSA) rats were euthanized 4 and 8 weeks after burn injury. The apoptosis profiles in the ventral horns of the lumbar spinal cords, sciatic nerves, and gastrocnemius muscles were examined. The Schwann cells in the sciatic nerve were marked with S100. The gastrocnemius muscles were harvested to measure the denervation atrophy.Result. The VHMNs apoptosis in the spinal cord was observed after inducing third-degree burns in the hindpaw. The S100 and TUNEL double-positive cells in the sciatic nerve increased significantly after the burn injury. Gastrocnemius muscle apoptosis and denervation atrophy area increased significantly after the burn injury.Conclusion. Local hindpaw burn induces apoptosis in VHMNs and Schwann cells in sciatic nerve, which causes corresponding gastrocnemius muscle denervation atrophy. Our results provided an animal model to evaluate burn-induced muscle wasting, and elucidate the underlying mechanisms.

Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.

Diabetic cardiomyopathy has been shown to promote hypertrophy, leading to heart failure. Recent studies have reported a correlation between diabetic cardiomyopathy and oxidative stress, suggesting that the accumulation of advanced glycation end products (AGEs) induces the production of reactive oxygen species (ROS). In a clinical setting, AGEs have been shown to increase the risk of cardiovascular disease; however, the relationship between AGEs and cardiac hypertrophy remains unclear. This study sought to identify the role of AGEs in cardiac hypertrophy by treating H9c2 cells with glyceraldehyde-derived AGEs (200 μg/ml) or H2O2 (50 μM) for 96 h. Our results demonstrate that AGEs significantly increased protein levels and cell size. These effects were effectively blocked with PD98059 (10 μM; MEK/ERK inhibitor) pretreatment, suggesting that AGEs caused cell hypertrophy via the MEK/ERK pathway. We then treated cells with AGEs and H2O2 for 0-120 min and employed the Odyssey infrared imaging system to detect MEK/ERK phosphorylation. Our results show that AGEs up-regulated MEK/ERK phosphorylation. However, this effect was blocked by NAC (5 mM; ROS inhibitor), indicating that AGEs regulate MEK/ERK phosphorylation via ROS. Our findings suggest that glyceraldehyde-derived AGEs are closely related to cardiac hypertrophy and further identify a molecular mechanism underlying the promotion of diabetic cardiomyopathy by AGEs.

Abdominal adhesions, whether caused by peritoneal trauma, radiation, infection, or a congenital condition, are associated with a wide range of complications. These complications include chronic abdominal or pelvic pain, infertility, and adhesive small bowel obstruction. Such adhesions render re-operation difficult, with attendant risks of inadvertent enterostomy and increased operation time. The purpose of this study was to investigate the potential of hyperbaric oxygen (HBO) therapy in the prevention of abdominal adhesions in an experimental animal study. A laparotomy was performed on Wistar rats to induce the formation of adhesions on the cecum and the intra-abdominal area (1 ´ 2 cm). A superficial layer of the underlying muscle from the right abdominal wall was also shaved and prepared for aseptic surgery. The rats were divided into four groups according to the duration of HBO therapy; five additional groups were designated according to the conditions of HBO therapy. When the rats were evaluated according to adhesion area and grade, a statistically significant difference was observed between the control and HBO treatment groups (p < 0.005). Results from this study suggest that HBO treatment could reduce adhesion formation; and further suggest that HBO therapy may have therapeutic potential in the treatment of postoperative peritoneal adhesion.

Objective Curcuminoids (including curcumin) are natural antioxidants demonstrating potent chemopreventive properties against several forms of cancer. This study investigated the antiproliferative and induced apoptotic effects of curcuminoids on three cell lines isolated from human breast adenocarcinoma and ductal carcinoma (MDA-MB-231, MDA-MB-435S, and MCF-7). Materials and Methods This study developed a highly sensitive, reproducible assay method using high-pressure liquid chromatography to quantify the cellular uptake of curcuminoids by breast cancer cells and quantitate its effect on inhibition of proliferation and activation of apoptosis in breast cancer cells. Results Results indicate that curcuminoids inhibited cell proliferation and activation of apoptosis in the cell lines in this study. Both effects were observed to increase in proportion to the cellular uptake of curcuminoids; cellular uptake increased following an increase in the dosage of curcuminoids. Conclusion The inhibition of proliferation and increased apoptosis of breast cancer cells appears to be associated with the uptake of curcuminoids by cancer cells.

Nasopharyngeal carcinoma (NPC) is one of the common malignant cancers in China, and radiotherapy or chemotherapy is the main therapy method for NPC. Curcuminoids (or curcumin), natural antioxidants, have been recently shown to produce a potent chemopreventive action against several types of cancer. They have also displayed antioxidant and anti-inflammatory activities. In the present study, the antiproliferation and induced apoptosis effects of curcuminoids have been investigated in Detroit 562 cells (human pharynx carcinoma) and HONE-1 (human nasopharyngeal carcinoma) cells. Results indicated that curcuminoids have produced an inhibition of cell proliferation as well as the activation of apoptosis in these cancer cells. Both effects were observed to increase in proportion with the dose of curcuminoids. The DNA fragmentation, caspase-3 activation,and NF-kappaB transcriptional factor activity have been studied. By these approaches, apoptosis was induced by curcuminoids in the pharynx and nasopharyngeal cancer cells via caspase-3-dependent pathway. However, a different dependency has been observed, whereas proliferation inhibition and apoptosis depend upon the amount of curcuminoid treatment in the cancer cells.

Curcumin, which is a bright orange-yellow pigment of turmeric with antioxidant properties, has been shown to produce a potent preventative action against several types of cancers in recent studies. It has also been reported to protect the development of colon tumor in animals being fed with carcinogen. In the colon cancer cells, curcumin was illustrated to inhibit cell proliferation and induce apoptosis. As an antioxidant, it acts as an anti-inflammatory as well as an antitumor agent. Curcumin has been detected to exist in nature in the form of curcuminoids, a mixture of curcumin, the major component, with two of its related demethoxy compounds (demethoxycurcumin and bisdemethoxycurcumin). In the present study, we have investigated the antiproliferation and induced apoptosis effects of curcuminoids on colon cancer, using the primary cancer cells isolated from Taiwanese colon cancer patients as the model for colorectal cancer. Results showed that curcuminoids inhibited cell proliferation and induced apoptosis of these human primary colon cancer cells. The effects were observed in a dose-dependent manner as dose increased from 12.5 to 100 microM. With the aim of furthering the fundamental understanding of the mechanisms underlying the antiproliferation and induced apoptosis effects of curcuminoids on these human colon cancer cells, we developed a sensitive, rapid, and reproducible assay method based on high-performance liquid chromatography (HPLC). This HPLC technique developed was found to successfully determine, in a quantitative manner, the cellular uptake of curcuminoids. The uptake of these curcuminoids by the colon cancer cells was shown to increase as the dose of curcuminoids was increased. The observations of inhibited proliferation and increased apoptosis in the colon cancer cells appeared to be associated with the cellular uptake of curcuminoids.

By studying the responses of nitric oxide in pulmonary fibrosis, the role of inducible nitric oxide synthase in diffuse pulmonary fibrosis as caused by lipopolysaccharide (LPS) treatment was investigated. When compared to rats treated with LPS only, the rats pretreated with 1400W (an iNOS-specific inhibitor) were found to exhibit a reduced level in: (i) NOx (nitrate/nitrite) production, (ii) collagen type I protein expression, (iv) soluble collagen production, and (iv) the loss of body weight and carotid artery PO2. In the pulmonary fibroblast culture, exogenous NO from LPS-stimulated secretion by macrophages or from a NO donor, such as DETA NONOate, was observed to induce the expression of TIMP-1, HSP47, TGF-beta1, and collagen type I as well as the phosphorylation of SMAD-2. After inhalation of NO for 24 h, an up-regulation of collagen type I protein was also noted to occur in rat pulmonary tissue. The results suggest that the NO signal pathway enhanced the expression of TGF-beta1, TIMP-1, and HSP47 in pulmonary fibroblasts, which collectively demonstrate that the NO signal pathway could activate the SMAD-signal cascade, by initiating a rapid increase in TGF-beta1, thereby increasing the expression of TIMP-1 and HSP47 in pulmonary fibroblasts, and play an important role in pulmonary fibrosis.

Keloids arise from the aberrant wound healing process and nitric oxide (NO) plays an important role in the inflammation stage of wound healing. In order to better define the potential effect of NO/cGMP signal pathway in the keloid pathogenesis, the enhancing effect of exogenous NO (released from NO donor) on collagen expression in the keloid fibroblast (KF) as well as on the induction of collagen type I protein and TGF-beta1 expression in the KF were studied in this investigation. The DETA NONOate, an NO donor, was added to the KF, as the exogenous NO, to release NO in the culture medium. The expression of collagens was then determined by assaying the total soluble collagens and collagen type I in the KF. The cellular concentration of cGMP was measured by EIA in the KF. Exogenous NO was found to enhance the expression of collagens and elevate the cellular levels of cGMP. Moreover, to evaluate the effect of the elevated cellular cGMP levels on the expression of collagen and TGF-beta1, both cGMP and TGF-beta1 were measured by ELISA. The inhibitors for phosphodiesterase (PDE), such as IBMX (3-isobutyl-1-methylxanthine), Vinpocetine, EHNA, Milrinone and Zapriast, which have been reported to reduce the ability of PDE and subsequently produce an increase of cellular cGMP, induce the production of autocrine TGF-beta1 as well as the synthesis of collagen in the KF. In this investigation, the inhibition of the PDE enzyme activity was observed to enhance the effect on the collagen synthesis, and was induced by exogenous NO. Taken together, these results have suggested that the NO/cGMP pathway could positively influence the progression of keloid formation, via the TGF-beta1 expression in the KF.

Nitric oxide (NO) has emerged as an important mediator of many physiological functions. Recent reports have shown that NO participates in the wound healing process, however, its role in keloid formation remains unclear. This study aimed to investigate the effect of NO on keloid fibroblasts (KF) and to determine the levels of inducible nitric oxide synthase (iNOS) expression in clinical specimens of keloid. Scar tissue from seven keloid patients with matched perilesion skin tissue controls was studied for inducible nitric oxide synthase expression and location. In addition, primary keloid and normal scar skin fibroblast cultures were set up to investigate the effects of NO in inducing collagen type I expression. Inducible nitric oxide synthase expression, and NO production were elevated in keloid scar tissues but not in matched perilesion skin tissues. Furthermore, exposure of KF to exogenous NO resulted in increased expression of collagen type I in a dose-dependent manner. NO exposure also induced time-course dependent collagen I expression that peaked at 24 h in KF. Taken together, these results indicate that excess collagen formations in keloid lesion may be attributed to iNOS overexpression.

Cervical cancer is one of the most common malignancies affecting women, and infection with high-risk HPV type 16 is a major cause of this cancer. This study investigates the influence of C-X-C chemokine receptor type 4 (CXCR4) on cervical carcinogenesis associated with HPV16 E6/7 infection, using primary cancer cells isolated from Taiwanese cervical cancer patients as a model for cervical cancer. We investigated the functional interaction between CXCR4 in Cx cells and HPV16 E6/7 transfected Cx cells (CxWJ cells), according to cell cycle, invasive ability and MMPs and CXCR4 gene expression. Our results indicate that the up-regulation of CXCR4 gene expression in CxWJ cells partially enhance proliferation and the invasive ability provided by HPV 16 E6/7 stimulation. These data provide evidence of a functional interaction between HPV16 E6/7 in CXCR4, suggesting that cooperative stimulation of HPV E6/7 in the up-regulation of CXCR4 in human cervical cancer cells may be necessary to completely overcome the oncogenic function associated with the progression of cervical carcinogenesis.

Nasopharyngeal carcinoma (NPC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound-based drug which from the climbing stem of Cucumic melo L (Guadi). Previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study, investigated anti-proliferation and cell cycle G2/M arrest induced by CuE in Detroit 562 cells (pharynx carcinoma) and HONE-1 (nasopharyngeal carcinoma) cells. Results indicate that the cytotoxicity is associated with accumulation in G2/M cell-cycle phases. CuE produced cell cycle arrest as well as the downregulation of cyclin B1 and CDC2 expression. In addition, treated cells with CuE and GADD45γ SiRNA that also coincided with GADD45γ gene activation in cell cycle arrest. Both effects increased proportionally with the dose of CuE; however, proliferation inhibition and mitosis delay was dependant on the amount of CuE treatment in the cancer cells.

A label-free and array-based optical liquid-crystal (LC) immunodetection technique for the detection of CA125 antigen, a protein biomarker most frequently used for ovarian cancer detection, was demonstrated with a nematic LC with larger birefringence (Δn) to promote sensitivity in detecting biomolecules. The LC-based immunodetection offers an alternative and sensitive approach for the detection of biomarker proteins, with the potential of replacing conventional immunoassays used in biochemical studies and clinical laboratories.

Background Malignant tumors are the single most common cause of death and the mortality rate of ovarian cancer is the highest among gynecological disorders. The excision of benign tumors is generally followed by complete recovery; however, the activity of cancer cells often results in rapid proliferation even after the tumor has been excised completely. Thus, clinical treatment must be supplemented by auxiliary chemotherapy or radiotherapy. Sulforaphane (SFN) is an extract from the mustard family recognized for its anti-oxidation abilities, phase 2 enzyme induction, and anti-tumor activity. Methods This study investigated the cell cycle arrest in G2/M by SFN and the expression of cyclin B1, Cdc2, and the cyclin B1/CDC2 complex in PA-1 cells using western blotting and co-IP western blotting. Results This study investigated the anticancer effects of dietary isothiocyanate SFN on ovarian cancer, using cancer cells line PA-1. SFN-treated cells accumulated in metaphase by CDC2 down-regulation and dissociation of the cyclin B1/CDC2 complex. Conclusion Our findings suggest that, in addition to the known effects on cancer prevention, SFN may also provide antitumor activity in established ovarian cancer.

Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G₁ phase due to the down-regulation of CDK 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer.

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities as well as potent chemopreventive action against cancer. The present study investigates the anti-proliferation (using MTT assay, SFN demonstrated cytotoxic activity against GBM 8401 cell with IC(50) values at 35.52 μM) and induced apoptosis of SFN 24-h treatment in the cells of human brain malignant glioma GBM 8401 cells. We studied the MMP, caspase, MEK/ERK activation, and NF-κB transcription factor activity. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects increased in proportion to the dosage of SFN, and apoptosis was induced via mitochondria- and caspase-dependent pathways. Daily s.c. injections of SFN for 3 weeks in severe combined immunodeficient mice (SCID) with GBM8401 s.c. tumors resulted in a decrease in mean tumor weight of 69-75 % compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, SFN may provide antitumor activity in established malignant glioma.

Demethoxycurcumin (DMC; a curcumin-related demethoxy compound) has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC50values at 22.71 μM) and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP), DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan; it ranks top three in the cancer mortality rate. Curcuminoids are derived from the rhizome of Curcuma longa. It has shown anti-cancer activity and apoptosis induction in a variety of cancer cell lines. This aims to study the potential of Poloxamer 407 as the thermogelling and mucoadhesive polymer for development of a site-targeting delivery system to enhance the localized delivery of curcuminoids to the colorectal cells for CRC chemotherapy.The mucoadhesive strength and rheological properties were measured as a function of poloxamer loaded with curcuminoids.The gelation temperature of Poloxamer 407 was found to vary with its concentration and start gelling at 37°C at the concentration of 15.5% (w/v). To ensure gelation at physiological temperature after intra-rectal application, gelation temperature was determined by rheological measurement as well as by its physical appearance. The results indicated that its mucoadhesive strength also shows a dependency on temperature, which appears to be related to the increment in the maximum strength and average strength of the polymer.The results have suggested that Poloxamer 407 could be a potential thermogelling and mucoadhesive polymer for the development of a site-targeting colorectal drug delivery system for curcuminoids in colorectal cancer therapy.

Cervical cancer is the most common malignancy in females worldwide. This study investigated the prevalence of the E6/E7 oncoproteins of human papillomavirus (HPV) type 16, which are important in fibroblast growth factor (FGF) 2- and 4-induced epithelial-mesenchymal transition (EMT) and cervical tumorigenesis. We investigated the functional interaction between HPV16 E6/E7-transfected Cx cells (CxWJ cells) and treatment with FGF2 and 4, according to the expression of α-smooth muscle actin (α-SMA), vimentin and E-cadherin protein as well as cell growth and invasive ability. The results showed the upregulation of α-SMA and vimentin and the downregulation of E-cadherin protein expression in CxWJ cells. HPV16 E6/E7 infection partially repressed proliferation, but not the invasive ability of FGF2 or FGF4 stimulation in cervical cancer cells (CxWJ cells). These data provide evidence of a functional interaction between HPV16 E6/E7 and FGFs 2 and 4, suggesting that cooperative stimulation of HPV E6/E7 and FGFs activated in human cervical cancer cells is required to completely overcome the oncogenic function associated with the development of cervical epithelial-mesenchymal transition and tumorigenesis.

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential(ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

Curcuminoids, natural plant components, have been recently shown to display antioxidant and anti-inflammatory activities. They also produce potent chemo-preventive action against several types of cancer. In the present study, the anti-proliferative and induced apoptosis effects of curcuminoids have been investigated in human brain glioblastoma multiforme (GBM) 8401 cells. Results indicated that curcuminoids have produced an inhibition of cell proliferation in a dose-dependent manner as dosage increased from 12.5 to 100 μM (n = 6) via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dose of curcuminoids. We have studied the mitochondrial membrane potential (ΔΨm), DNA fragmentation, caspase-3, caspase-8, and caspase-9 activation, and nuclear factor κB (NF-κB) transcriptional factor activity to analyze apoptosis in GBM 8401 cells. From these approaches, apoptosis was induced by curcuminoids in human brain GBM 8401 cells via mitochondria and a caspase-dependent pathway. The results observed with proliferation inhibition (y = 94.694e(-0.025x), R(2) = 0.9901, and n = 6) and apoptosis (y = 0.9789e(-0.0102x), R(2) = 0.99854, and n = 3) depend upon the amount of curcuminoid treatment in the cancer cells.

Summary Background The excessive accumulation of extracellular matrix is a hallmark of many fibrotic diseases, including the hypertrophic scar and keloid. Recent reports from this research team had shown that exogenous nitric oxide (NO) participates in the keloid formation; however, its role on the synthesis of fibrotic factor (TGF-β1, TIMP-1 and HSP47) in the keloid fibroblasts (KF) remained unclear. Objective In this study, to better define the potential effect of exogenous NO on the expression of fibrotic factors in KF, the enhancing effect of exogenous NO, released from a NO donor, on the synthesis of fibrotic factors in KF was investigated. Methods The seven primary KF cultures were set up to measure the effect of exogenous NO on enhancing the expression of fibrotic factor. Results Elevation of cellular cGMP levels was observed to be induced by NO or blocked by the hydrolysis activity of phosphodiesterase (PDE) by the PDE inhibitor. The elevated levels of cellular cGMP were noted to enhance the expression of TIMP-1 and HSP47 in KF. Exogenous NO was found to significantly accelerate the production of TIMP-1 and HSP47 in the seven primary KFs with a corresponding increase in the production of TGF-β1. Conclusion The results have led to a conclusion, that is: the excess collagen formations in the keloid lesion may be attributed to the NO/cGMP signal pathway by initiating a rapid increase in the expression of TGF-β1, TIMP-1 and HSP47 in the KF cells.