Induction of solid tumor growth inhibition induced by a differentiation inducer cotylenin A and molecular target agents and its molecular mechanism

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Shimane University
• Principal Investigator: KASUKABE Takashi 島根大学, 学術研究院医学・看護学系, 特任教授 (50152658)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: コチレニンA / 分化誘導剤 / 活性酸素誘導剤 / 膵癌細胞 / 併用効果 / フェロトーシス / アポトーシス

Outline of Final Research Achievements

We have examined whether a new differentiation inducer of leukemia cells can suppress the proliferation of solid tumor cells. In this study we found that cotylenin A plus phenethyl isothiocyanate (PEITC), an inducer of reactive oxygen species(ROS) and a dietary anticarcinogenic compound, or piperlongumine (PL), a natural product with cytotoxic properties restricted to cancer cells, synergistically inhibited the proliferation of human pancreatic cancer cells. The combined treatment with CN-A plus PEITC or PL synergistically induced the generation of ROS. Antioxidants, ferroptosis inhibitors and iron chelators canceled the synergistic cell death. These results show that synergistic cell death induced by the combined treatment with CN-A plus PEITC or PL is mainly due to the induction of ferroptosis. These results suggest that the combination of CN-A plus PEITC or PL has potential as a novel therapeutic strategy against pancreatic cancer.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究ではコチレニンＡとある種の活性酸素誘導剤で難治性の膵癌細胞に対してフェロトーシスを介した細胞死を誘導できること見出した。フェロトーシスはアポトーシスやネクロトーシスとは異なる機序で誘導される新規の細胞死であり、これまでの抗癌剤に耐性となった癌細胞に対してもフェロトーシスを介した細胞死を誘導できる可能性が示唆されている。現時点では、フェロトーシス誘導剤の報告は少なく、フェロトーシス誘導による新たな膵癌治療法を確立するためにも、膵癌細胞のフェロトーシス誘導剤を見出すことは意味があると考えられた。