Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis

International Journal of Molecular Sciences

Jung-Hyun Shim¹  Goo Yoon¹  So-Yeon Park²  ChathurikaD. B. Gamage²  Yi Yang²  Hangun Kim²  İsa Taş²  Rui Zhou²  Eunae Kim³  WooKyun Bae⁴  KyungKeun Kim⁵ 

[1] College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, 1666 Yeongsan-ro, muan, Jeonnam 58554, Korea;College of Pharmacy and Research Institute of Life and Pharmaeutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea;College of Pharmacy, Chosun University, 309 Philmun-daero, Dong-gu, Gwangju 61452, Korea;Department of Internal Medicine, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea;Department of Pharmacology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea;

关键词: deoxypodophyllotoxin;    tubulin polymerization;    apoptosis;    mitotic arrest;    tumorigenic potentials;    colorectal cancer;   

DOI  :  10.3390/ijms20112612

来源: DOAJ

【 摘 要 】

Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.

【 授权许可】

Unknown