hispidin and Pancreatic-Neoplasms

Natural products extracted from plants can be potent for developing pharmaceutical products. Hispidin, a polyphenolic compound mainly derived from the medicinal mushroom Phellinus linteus, has been shown to have a therapeutic potential against cancer cells. Pancreatic cancer is one of the most aggressive solid malignancies with high resistance to existing drugs. Cancer stem cells (CSCs) are responsible for chemoresistance. The present study aimed to evaluate the anticancer effects of hispidin on pancreatic CSCs.. The cytotoxic effects of hispidin on BxPC-3 and AsPC-1 pancreatic cancer cells and BxPC-3 CD44. Hispidin exerted antitumor effects against both BxPC-3 pancreatic cancer cells and CSCs. Furthermore, it was found that hispidin sensitized pancreatic CSCs to gemcitabine and promoted the therapeutic efficacy of gemcitabine.. Hispidin might be a novel chemosensitizer for gemcitabine and a potential synergistic agent for increasing the therapeutic index of gemcitabine as a treatment for pancreatic cancer.

Topics: Blotting, Western; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Down-Regulation; Drug Resistance, Neoplasm; Gemcitabine; Humans; Neoplastic Stem Cells; Pancreatic Neoplasms; Pyrones

The trypanocidal activity of naturally occurring 6-(3,4-dihydroxystyryl)-4-hydroxy-2-pyrone (hispidin) prompted us to examine its cytotoxic activity toward normal and cancerous cells in culture. Hispidin synthesized in our laboratory to a high degree of purity (checked by 1H and 13C NMR spectroscopy) was shown to be cytotoxic (between 10(-3) mol/L and 10(-7) mol/L) toward normal human MRC-5 fibroblasts, human cancerous keratinocytes (SCL-1 cell line), and human cancerous pancreatic duct cells (Capan-1 cell line). Interestingly, addition of hispidin in three successive doses (between 10(-5) mol/L and 10(-7) mol/L) led to a 100-fold increase in activity with an enhanced activity on cancer cells compared to normal cells (50%). Synthetic hispidin was found to inhibit isoform beta of protein kinase C (IC50 of 2 x 10(-6) mol/L), but not E. coli and placental type XV alkaline phosphatases. The enhanced activity of hispidin toward the cancerous cell lines is discussed.

Topics: Adenocarcinoma; Adult; Alkaline Phosphatase; Antineoplastic Agents; Basidiomycota; Carcinoma, Squamous Cell; Cell Line; Drug Screening Assays, Antitumor; Facial Neoplasms; Fibroblasts; Growth Inhibitors; Humans; Keratinocytes; Lung; Male; Pancreatic Neoplasms; Protein Kinase C; Pyrones; Tumor Cells, Cultured