Dong Guang-Zhi, Jeong Ji Hye, Lee Yu-Ih, Lee So Yoon, Zhao Hui-Yuan, Jeon Raok, Lee Hwa Jin, Ryu Jae-Ha
Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
Department of Natural Medicine Resources, Semyung University, 65 Semyung-Ro, Jecheon, Chungbuk, 390-711, Republic of Korea.
Arch Pharm Res. 2017 Apr;40(4):509-517. doi: 10.1007/s12272-017-0905-2. Epub 2017 Mar 3.
Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.
胰腺癌是主要的癌症病因之一，其5年生存率最低。有必要研发更有效的抗胰腺癌药物，以克服其快速转移以及对手术、放疗、化疗及这些治疗方法联合使用的耐药性。我们已从高良姜和日本桤木中鉴定出几种二芳基庚烷类化合物作为抗胰腺癌药物。这些二芳基庚烷类化合物抑制胰腺癌细胞（PANC-1）的细胞增殖并诱导其细胞周期停滞。其中，最有效的化合物1和7抑制PANC-1细胞中的shh-Gli-FoxM1信号通路及其靶基因表达。此外，它们抑制了细胞周期相关基因的表达，而外源性FoxM1的过表达可挽救这些基因的表达。综上所述，高良姜中的（E）-7-（4-羟基-3-甲氧基苯基）-1-苯基庚-4-烯-3-酮（1）和日本桤木中的阔叶枫香烯酮（7）通过抑制shh-Gli-FoxM1信号通路抑制PANC-1细胞增殖，它们可能是抗胰腺癌药物研发的潜在候选物。
