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Background/Objectives: Luteolin (LUT) is a natural flavonoid with known anti-inflammatory, antioxidant, and anti-cancer properties. Cervical cancer, particularly prevalent in certain regions, remains a significant health challenge due to its high recurrence and poor response to treatment. This study aimed to investigate the anti-tumor effects of LUT on human cervical epidermoid carcinoma cells (Ca Ski), focusing on cell growth inhibition, apoptosis induction, and regulation of mitochondrial membrane potential. Methods: Ca Ski cells were treated with varying concentrations of LUT (0, 25, 50, 100 µM) for different time periods (24, 48, 72 hours). Cell viability was measured using the MTT assay, apoptosis was assessed by flow cytometry with annexin V-FITC/PI staining, and changes in mitochondrial membrane potential were evaluated using JC-1 staining. Caspase-3 activation was examined by flow cytometry, and expression of apoptosis-related proteins (caspase-3, -8, -9, AIF) was analyzed via Western blotting. Results: LUT significantly inhibited the growth of Ca Ski cells in a dose- and time-dependent manner, with the most pronounced effects observed at 100 µM over 72 hours. Flow cytometry confirmed that LUT induced apoptosis without causing necrosis. Mitochondrial membrane potential was reduced after LUT treatment, coinciding with increased caspase-3 activation. Western blot analysis revealed the upregulation of pro-apoptotic proteins caspase-3, -8, -9, and AIF, indicating that LUT induces apoptosis through the intrinsic mitochondrial pathway. Conclusions: Luteolin effectively inhibits cervical cancer cell proliferation and induces apoptosis by disrupting mitochondrial membrane potential and activating caspases. These findings suggest that LUT holds potential as a therapeutic agent for cervical cancer, with further studies needed to explore its in vivo efficacy and broader clinical applications.

Glioblastoma multiforme (GBM) is a highly aggressive and devastating brain tumor characterized by poor prognosis and high rates of recurrence. Despite advances in multidisciplinary treatment, GBM constinues to have a poor overall survival. The Radix Glycyrrhizae Preparata (RGP) has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory activities. However, it not clear what effect it may have on tumorigenesis in GBM. This study demonstrated that RGP reduced glioma cell viability and attenuated glioma cell locomotion in GBM8401 and U87MG cells. RGP treated cells had significant increase in the percentage of apoptotic cells and rise in the percentage of caspase-3 activity. In addition, the results of study’s cell cycle analysis also showed that RGP arrested glioma cells at G2/M phase and Cell failure pass the G2 checkpoint by RGP treatment in GBM8401 Cells. Based on the above results, it seems to imply that RGP activated DNA damage checkpoint system and cell cycle regulators and induce apoptosis in established GBM cells. In conclusion, RGP can inhibit proliferation, cell locomotion, cell cycle progression and induce apoptosis in GBM cells in vitro.

Cucurbitacin I (JSI-124), derived from Cucurbitaceae, has shown the potential to induce apoptosis and cell cycle arrest in some cancer cells. However, the effect of JSI-124 on glioblastoma multiforme (GBM) cell cycle and apoptosis is still unclear. Our investigation revealed that JSI-124 effectively reduced cell viability in GBM cells, leading to apoptosis and increased caspase-3 activity. Intriguingly, JSI-124 caused the accumulation of G2/M phase to regulate cell cycle, confirmed by MPM-2 staining and increased protein synthesis during mitosis by mitotic index analysis. Western blot analysis found that JSI-124 affected the progression of G2/M arrest by downregulating the CDK1 and upregulating the cyclinB1, suggesting that JSI-124 disrupted the formation and function of the cyclin B1/CDK1 complex in GBM8401 and U87MG cells. However, we found the JSI-124-regulated cell cycle G2/M and apoptosis-relative gene in GBM8401 and U87MG cells by NGS data analysis. Notably, we found that the GBM8401 and U87MG cells observed regulation of apoptosis and cell-cycle-related signaling pathways. Taken together, JSI-124 exhibited the ability to induce G2/M arrest, effectively arresting the cell cycle at critical stages. This arrest is accompanied by the initiation of apoptosis, highlighting the dual mechanism of action of JSI-124. Collectively, our findings emphasize that JSI-124 holds potential as a therapeutic agent for GBM by impeding cell cycle progression, inhibiting cell proliferation, and promoting apoptosis. As demonstrated by our in vitro experiments, these effects are mediated through modulation of key molecular targets.

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA) has antioxidant and anti-inflammatory activities; however, whether CDDO-dhTFEA has anticancer effects is unclear. The objective of this research was to investigate the possibility of CDDO-dhTFEA as a potential cancer-fighting treatment in glioblastoma cells. Our experiments were performed on U87MG and GBM8401 cells, and we found that CDDO-dhTFEA was effective in reducing cell proliferation in both cell lines, in a manner that was dependent on both time and concentration. Additionally, we observed that CDDO-dhTFEA had a significant impact on the regulation of cell proliferation, which was evident in the increase in DNA synthesis that was observed in both cell types. CDDO-dhTFEA induced G2/M cell cycle arrest and mitotic delay, which may be associated with the inhibition of proliferation. Treatment with CDDO-dhTFEA led to cell cycle G2/M arrest and inhibited proliferation of U87MG and GBM8401 cells by regulating G2/M cell cycle proteins and gene expression in GBM cells in vitro.

Our research has revealed that sulforaphane (SFN) has chemopreventive properties and could be used in chemotherapy treatments. Further investigation is needed to understand the mechanisms behind sulforaphane’s (SFN) antitumor activity in breast adenocarcinoma, as observed in our studies. This research looked into the effects of SFN on mitosis delay and cell cycle progression in MDA-MB-231 and ZR-75-1 cells, two types of triple-negative breast cancer adenocarcinoma.The proliferation of the cancer cells after SFN exposure was evaluated using MTT assay, DNA content and cell cycle arrest induction by flow cytometry, and expressions of cdc25c, CDK1, cyclin B1 and CDK5R1 were assessed through qRT-PCR and Western blot analysis. SFN was found to inhibit the growth of cancer cells. The accumulation of G2/M-phase cells in SFN-treated cells was attributed to CDK5R1. The disruption of the CDC2/cyclin B1 complex suggested that SFN may have antitumor effects on established breast adenocarcinoma cells. Our findings suggest that, in addition to its chemopreventive properties, SFN could be used as an anticancer agent for breast cancer, as it was found to inhibit growth and induce apoptosis of cancer cells.

RTA dh404 is a novel synthetic oleanolic acid derivative that has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory properties, and exerts therapeutic effects on various cancers. Although CDDO and its derivatives have anticancer effects, the actual anticancer mechanism has not been fully explored. Therefore, in this study, glioblastoma cell lines were exposed to different concentrations of RTA dh404 (0, 2, 4, and 8 µM). Cell viability was evaluated using the PrestoBlue™ reagent assay. The role of RTA dh404 in cell cycle progression, apoptosis, and autophagy was analyzed using flow cytometry and Western blotting. The expression of cell cycle-, apoptosis-, and autophagy-related genes was detected by next-generation sequencing. RTA dh404 reduces GBM8401 and U87MG glioma cell viability. RTA dh404 treated cells had a significant increase in the percentage of apoptotic cells and caspase-3 activity. In addition, the results of the cell cycle analysis showed that RTA dh404 arrested GBM8401 and U87MG glioma cells at the G2/M phase. Autophagy was observed in RTA dh404-treated cells. Subsequently, we found that RTA dh404-induced cell cycle arrest, apoptosis, and autophagy were related to the regulation of associated genes using next-generation sequencing. Our data indicated that RTA dh404 causes G2/M cell cycle arrest and induces apoptosis and autophagy by regulating the expression of cell cycle-, apoptosis-, and autophagy-related genes in human glioblastoma cells, suggesting that RTA dh404 is a potential drug candidate for the treatment of glioblastoma.

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.

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that another two tumor suppressor genes, NOTCH1 and FAT1, have a high nonsense mutation rate in head and neck squamous cell carcinoma (HNSCC). PTC124 may re-express the functional NOTCH1 or FAT1 in nonsense mutation NOTCH1 or FAT1 in HSNCC (2) Methods: DOK (with NOTCH1 Y550X) or HO-1-u-1 (with FAT1 E378X) HNSCC cells were treated with PTC124, and the NOTCH1 or FAT1 expression, cell viability, and NOTCH1- or FAT1-related downstream gene profiles were assayed. (3) Results: PTC124 was able to induce NOTCH1 or FAT1 expression in DOK and HO-1-u-1 cells. PTC124 was able to upregulate NOTCH downstream genes HES5, AJUBA, and ADAM10 in DOK cells. PTC124 enhanced DDIT4, which is under the control of the FAT1–YAP1 pathway, in HO-1-u-1 cells. FLI-06 (a NOTCH signaling inhibitor) reversed PTC124-mediated cell growth inhibition in DOK cells. PTC124 could reverse TT-10 (a YAP signaling activator)-mediated HO-1-u-1 cell proliferation. (4) Conclusions: PTC124 can rescue nonsense mutation of NOTCH1 and FAT1 to repress HNSCC cell proliferation.

The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

The p53 family has the following three members: p53, p63 and p73. p53 is a tumor suppressor gene that frequently exhibits mutation in head and neck cancer. Most p53 mutants are loss-of-function (LoF) mutants, but some acquire some oncogenic function, such as gain of function (GoF). It is known that the aggregation of mutant p53 can induce p53 GoF. The p73 activators RETRA and NSC59984 have an anti-cancer effect in p53 mutation cells, but we found that p73 activators were not effective in all head and neck squamous cell carcinoma (HNSCC) cell lines, with different p53 mutants. A comparison of the gene expression profiles of several regulator(s) in mutant HNSCC cells with or without aggregation of p53 revealed that nicotinamide phosphoribosyltransferase (NAMPT) is a key regulator of mutant p53 aggregation. An NAMPT inhibitor, to reduce abnormal aggregation of mutant p53, used in combination with a p73 activator, was able to effectively repress growth in HNSCC cells with p53 GoF mutants. This study, therefore, suggests a potential combination therapy approach for HNSCC with a p53 GoF mutation.