Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer and exhibits a devastating 5-year survival rate. The most recent procedure for the treatment of PDAC is a combination of several conventional chemotherapeutic agents, termed FOLFIRINOX, that includes irinotecan, leucovorin, oxaliplatin, and 5-fluorouracil (5-FU). However, ongoing treatment using these agents is challenging due to their severe side effects and limitations on the range of patients available for PDAC. Therefore, safer and more innovative anticancer agents must be developed. The anticarcinoma activity of matairesinol that can be extracted from seagrass has been reported in various types of cancer, including prostate, breast, cervical, and pancreatic cancer. However, the molecular mechanism of effective anticancer activity of matairesinol against pancreatic cancer remains unclear. In the present study, we confirmed the inhibition of cell proliferation and progression induced by matairesinol in representative human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). Additionally, matairesinol triggers apoptosis and causes mitochondrial impairment as evidenced by the depolarization of the mitochondrial membrane, disruption of calcium, and suppression of cell migration and related intracellular signaling pathways. Finally, matairesinol exerts a synergistic effect with 5-FU, a standard anticancer agent for PDAC. These results demonstrate the therapeutic potential of matairesinol in the treatment of PDAC.     

儿茶素单体EGC对胰脂肪酶的抑制作用及其机理研究

为研究儿茶素单体表没食子儿茶素（Epigallocatechin,EGC）对胰脂肪酶的抑制作用及机制,以干燥绿茶为原料,采用热水提取法、三氯甲烷脱色素和柱层析分离,得到EGC单体。采用扫描电子显微镜、傅里叶红外光谱、核磁共振氢谱对纯化的EGC单体进行结构表征,再通过滴定法研究EGC对胰脂肪酶的抑制作用及类型,然后通过荧光光谱法以及分子对接技术表征了EGC对胰脂肪酶结构的影响。结果表明,EGC以非竞争性方式对胰脂肪酶表现出抑制作用,并且抑制效果随EGC浓度的增加呈持续上升趋势,半抑制浓度为(1.62±0.085) mg·mL^-1。EGC对胰脂肪酶有荧光猝灭作用,可通过分子间氢键和疏水相互作用与酶中的氨基酸残基结合,导致酶的化学结构和空间构象发生变化,从而降低酶活性。EGC主要通过改变胰脂肪酶的化学结构和空间构象来抑制该酶活性,从而达到降血脂功效。