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A new schiff base cobalt(III) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC 50 is in the range of 6.27-22.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

A new Schiff base copper(II) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC 50 (50% inhibition concentrations) is in the range of 5.13-11.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Krüppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients' tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.

Sphingolipids are a class of lipids that have important signaling functions. The most widely studied bioactive shingolipids include ceramides, sphingosine-1-phosphate and so on. In contrast, dihydroceramides have received poor attention. However, recent reports indicate that dihydroceramides are in fact bioactive lipids. The biological activity of dihydroceramide derivatives have been proven in the biophysical, genetic and pharmacological models by decreasing dihydroceramide desaturase activity. Current research shows that dihydroceramides are involved in a variety of important physiological and pathological processes, including the response of autophagy, apoptosis and cell cycle arrest. In this review article, we summarizes the recent advances in study of dihydroceramide in the metabolism pathway, the key metabolic enzymes and biological funcitons.

Cell apoptosis induced by Angiotensin II (Ang II) has a critical role in the development of cardiovascular diseases. The aim of the present study was to investigate whether sanguinarine (SAN), a drug which was proved to have anti‑oxidant, anti‑proliferative and immune enhancing effects, can abolish cell apoptosis induced by Ang II. In the present study, H9c2 cardiac cells were stimulated with 10 µM Ang II with or without SAN. The level of intracellular reactive oxygen species (ROS) generation was assessed using dichlorodihydrofluorescein diacetate, and changes of the mitochondrial membrane potential (MMP) were assessed using JC‑1 staining. Furthermore, mRNA expression of NOX2 was determined by reverse transcription quantitative polymerase chain reaction, and apoptosis was detected by Annexin V/propidium iodide staining and flow cytometry. The expression of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) as well as cleaved (c)‑caspase 3 and ‑9 were detected by western blot analysis, and the activity of caspase 3 and ‑9 was detected using an ELISA. The results of the present study showed that NOX2 expression and ROS generation induced by Ang II were inhibited by SAN, and the Ang 2‑induced MMP loss was also ameliorated. Furthermore, Ang II‑induced H9c2 cardiac cell apoptosis as well as c‑caspase 3 and ‑9 levels were significantly reduced by SAN. Investigation of the possible pathway involved in the anti‑apoptotic effect of SAN showed that the expression of Bcl‑2 was decreased, while that of Bax was increased following stimulation with Ang II, which was reversed following treatment with SAN. In addition, Ang II enhanced the activity of caspase 9 and cleaved downstream caspases such as caspase‑3, initiating the caspase cascade, while pre‑treatment of H9c2 cardiac cells with SAN blocked these effects. In conclusion, the findings of the present study indicated that SAN inhibits the apoptosis of H9c2 cardiac cells induced by Ang II, most likely via restoring ROS‑mediated decreases of the MMP.

Pachymic acid (PA), a lanostane-type triterpenoid and the major component of Poria cocos alcoholic extracts, has various pharmacological effects, including anti-inflammatory, anti-oxidative and anti-apoptotic. However, few studies have investigated the effects of PA on lipopolysaccharide (LPS)-induced H9c2 cell apoptosis and inflammation, or identified the possible mechanisms underlying these effects. In the present study, H9c2 cardiomyocytes were stimulated by LPS and treated with or without PA. The increased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1 and IL-6 induced by LPS were attenuated following treatment with PA. PA also attenuated LPS-induced apoptosis, as determined by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and regulated the LPS-induced protein expression levels of caspase 3, 8 and 9. Furthermore, the phosphorylations of extracellular-regulated kinase (Erk)1/2 and p38 in the LPS-treated H9c2 cells were inhibited by PA. These results suggested that treatment with PA prevented the LPS-induced inflammatory and apoptotic response in cardiomyocytes, which may be mediated by inhibition of the Erk1/2 and p38 pathways.

Neuroblastoma is a solid tumor of the sympathetic nervous system accounting for up to 10% of pediatric cancers and 15% of cancer-related deaths. It is a useful system for investigation of stress signal-mediated apoptosis as a tumor suppression mechanism. In this study, we present evidence that p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway. In summary, we define a molecular pathway for mediating DNA damaging drug-induced apoptosis in human neuroblastoma IMR32 cells and suggest that inactivation of essential components of this apoptotic pathway may confer drug resistance on neuroblastoma cells.

Aim: This study aimed to investigate the function of long noncoding RNA RHPN1 antisense RNA 1 (lncRNA RHPN1‐AS1) in the progression of endometrial cancer (EC) and its underlying molecular mechanisms. Methods: The RHPN1‐AS1 expression was measured by quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) in EC tissues and cells. The cell clones, proliferation, cell cycle, apoptosis, migration and invasion in Ishikawa and HEC‐1A cells were respectively measured by colony formation assay, cell counting kit‐8 assay (CCK‐8) assay, flow cytometry, wound healing assay and transwell assay. In addition, the protein expressions in Ishikawa and HEC‐1A cells were measured using western blot and Immunofluorescence assay. Results: Our data showed the RHPN1‐AS1 expression was significantly upregulated in both EC tissues and cells. The expression of RHPN1‐AS1 was significantly correlated with FIGO stage, histological grade, and lymph node metastasis. Additionally, silencing RHPN1‐AS1 could inhibit proliferation, cell cycle progression, migration and invasion, and also promote apoptosis in Ishikawa and HEC‐1A cells. Moreover, silencing RHPN1‐AS1 could markedly elevate the expressions of caspase‐3 and Bax, but reduce the Bcl‐2 expression in Ishikawa and HEC‐1A cells. We also found that silencing RHPN1‐AS1 could significantly inhibit the phosphorylation of MEK and ERK in Ishikawa and HEC‐1A cells. After U0126 pretreatment, the inhibition effect of silencing RHPN1‐AS1 on the phosphorylation of MEK and ERK was strengthened. Conclusion: Our study demonstrated that RHPN1‐AS1 could facilitate cell proliferation, migration and invasion, as well as inhibit apoptosis via activating ERK/MAPK pathway in EC. [ABSTRACT FROM AUTHOR]