Department of Biotechnology, Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
Mar Drugs. 2022 Jul 25;20(8):473. doi: 10.3390/md20080473.
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.
胰腺导管腺癌 (PDAC) 是最具侵袭性的癌症之一，其 5 年生存率极低。目前治疗 PDAC 的最新方法是联合几种传统化疗药物，即 FOLFIRINOX，其中包括伊立替康、亚叶酸、奥沙利铂和 5-氟尿嘧啶 (5-FU)。然而，由于这些药物具有严重的副作用且适用的 PDAC 患者范围有限，因此持续使用这些药物具有挑战性。因此，必须开发更安全、更具创新性的抗癌药物。从海草中提取的马胎素具有抗癌活性，已在包括前列腺癌、乳腺癌、宫颈癌和胰腺癌在内的多种癌症中得到报道。然而，马胎素对胰腺癌的有效抗癌活性的分子机制尚不清楚。在本研究中，我们证实了马胎素在代表性的人胰腺癌细胞系（MIA PaCa-2 和 PANC-1）中抑制细胞增殖和进展。此外，马胎素触发细胞凋亡并导致线粒体损伤，表现为线粒体膜去极化、钙破坏以及细胞迁移和相关细胞内信号通路的抑制。最后，马胎素与标准 PDAC 抗癌药物 5-FU 具有协同作用。这些结果表明马胎素在治疗 PDAC 方面具有治疗潜力。
