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Sesquiterpene lactones are bioactive compounds that have been identified as responsible for the anticancer activity of the medicinal herb, Inula helenium L. (IHL). However, the mechanisms of action involved in the anti‑pancreatic cancer activity of IHL have yet to be elucidated. The present study used an optimized extraction strategy to obtain sesquiterpene lactones from IHL (the resulting product termed ethyl acetate extract of IHL; EEIHL), and examined the potential mechanisms involved in the anti‑pancreatic cancer activity of EEIHL. Ethanol and ethyl acetate were used to extract sesquiterpene lactones from IHL to give the final product EEIHL. Cell Counting Kit‑8, colony formation and Annexin V/propidium iodide assays were used to detect the anti‑proliferative activity of EEIHL. Cell migration was determined with a wound healing assay. mRNA and protein expression levels were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. It was identified that low concentrations of EEIHL caused CFPAC‑1 cell cycle arrest in the G0/G1 phase, whereas high concentrations of EEIHL induced mitochondria‑dependent apoptosis. In addition, EEIHL could inhibit the phosphorylation of the signal transducer and activator of transcription (STAT)3/AKT pathway, potentially resulting in impeded cell mobility. In conclusion, EEIHL could activate mitochondrial‑dependent apoptosis and inhibit cell migration through the STAT3/AKT pathway in CFPAC-1 cells. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is one of the main treatments for pancreatic cancer, but radiation resistance limits its clinical application. As a result, novel therapeutic agents to improve radiosensitivity are urgently needed. This study aimed to investigate the effect of Ibr-7 (a derivative of ibrutinib) on the radiosensitivity of human pancreatic cancer cells. Methods: The effect of Ibr-7 on pancreatic cancer cell proliferation was detected by CCK-8 assays. Radiosensitivity was assessed by clonogenic formation assays. Cell cycle and cell apoptosis were analysed by flow cytometry. DNA damage was evaluated by immunofluorescence analysis. The expression levels of PARP, Cleaved caspase 3, p-EGFR and EGFR were determined by western blot. Results: Ibr-7 showed an anti-proliferative effect on PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 μmol/L) enhanced the effect of radiation on PANC-1 and Capan2 cells. Further findings showed that this combination enhanced G2/M phase arrest and increased cell apoptosis. Additional molecular mechanism studies revealed that the expression of p-EGFR was decreased by Ibr-7 alone or in combination with radiation. Overexpression of p-EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in the Ibr-7 plus radiation group. Conclusions: Our study indicated the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Background: The anti-tumor effects of S-allylcysteine (SAC), a water-soluble garlic derivative, on human ovarian cancer cells have been previous studied in vitro and in vivo models but the precise epigenetic molecular mechanisms are still unclear. This study aimed to investigate the epigenetic mechanism of SAC. Methods: Human epithelial ovarian cancer cell line A2780 was selected. Cell proliferation and cell cycle was analyzed. DNA methylation, DNA methyltransferase (DNMT) activity, tumor suppressor gene expressions, as well as protein expression were analyzed. Results: SAC could inhibit the proliferation of A2780 cells in dose- and time-dependent manners (the IC50 was 16.25 mmol/L and 5.25 mmol/L at 48 h and 72 h). Treatment of A2780 cells with SAC resulted in G1/S phase arrest. SAC treatment decreased global DNA methylation levels in A2780 cells in a dose-dependent manner. SAC decreased the levels of 5-methylcytosine, DNMT activity, messenger RNA (mRNA) and protein levels of DNMT1. Additionally, SAC treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor gene CDKN1A accompany with reduced cell division control 2 expression. Conclusion: Our data indicated the potential therapeutic effects of SAC on the human ovarian carcinoma cell line A2780 in vitro. The epigenetic mechanism of action of SAC may have important implications for epigenetic therapy. [ABSTRACT FROM AUTHOR]

Radiotherapy is an effective treatment for pancreatic cancer. However, radio-resistance often resulted in poor prognostic. Ibrutinib is an orally small molecule drug in B cell malignancies. Here, we investigated for the first time the effect of ibrutinib on radio-sensitivity of human pancreatic cancer cells in vitro and the potential mechanism involved in it. Human BXPC3 and Capan2 cell lines were treated with ibrutinib, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed after treated with ibrutinib and (or) radiation by clone formation assay. The cell cycle and cell apoptosis were measured by flow cytometry. Protein levels was analyzed by western blot. The results revealed that ibrutinib inhibited the proliferation of pancreatic cancer cells. Ibrutinib enhanced the effect of radiation with a sensitization enhancement ratio (SER) of 1.34, 1.68 in BXPC3 and Capan2 cells respectively. Ibrutinib combined with radiation induced G2/M arrest and cell apoptosis. Further investigations revealed that ibrutinib decreased the phosphorylation of EGFR, then reversed the upregulation of p-AKT and downstream genes by radiation. In conclusion, these results suggested that ibrutinib might be an excellent radiosensitizer in pancreatic cancer. [ABSTRACT FROM AUTHOR]