title: Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation.
abstract: To explore the cytotoxic mechanism of abrin P2 on human colon cancer HCT-8 cells, abrin P2 was isolated from the seed of Abrus precatorius L. It was found that abrin P2 exhibited cytotoxicity toward 12 different human cancer cell lines. Our results demonstrated that abrin P2 suppressed the proliferation of human colon cancer cells (HCT-8 cells) and induced cell cycle arrest at the S and G2/M phases. The mechanism by which abrin P2 inhibited cell proliferation was via the down-regulation of cyclin B1, proliferating cell nuclear antigen and Ki67, as well as the up-regulation of P21. In addition, abrin P2 induced a dose- and time-dependent increase in the rate of HCT-8 cell apoptosis. Treatment with both Z-VAD-FMK, a broad-spectrum caspase inhibitor, and abrin P2 demonstrated that abrin P2 induced HCT-8 cell apoptosis via the activation of caspases. Together, our results revealed that abrin P2-induced apoptosis in HCT-8 cells was associated with the activation of caspases-3/-8/-9, the reduction in the Bcl-2/Bax ratio, the loss of mitochondrial membrane potential, and the increase in cytochrome c release. We further showed that abrin P2 administration effectively suppressed the growth of colon cancer xenografts in nude mice. This is the first report that abrin P2 effectively inhibits colon cancer cell growth in vivo and in vitro by suppressing proliferation and inducing apoptosis.
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China Center of Research on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
authors.forename: Runmei
authors.initials: R
authors.lastname: Yang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China Center of Research on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China Center of Research on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Qin
authors.affiliation: Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Research Institute of Chemical Defense of PLA, Beijing 102205, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Life Sciences, Peking University, Beijing 100871, China gaonann@126.com rqfeng@pku.edu.cn.
authors.forename: Renqing
authors.initials: R
authors.lastname: Feng
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China gaonann@126.com rqfeng@pku.edu.cn.
authors.forename: Nannan
authors.initials: N
authors.lastname: Gao
mesh_terms: D000036:Abrin / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000036:Abrin; D020169:Caspases
keywords: abrin P2; apoptosis; caspase; cell proliferation; colon cancer