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Open AccessArticle

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

1
College of Pharmacy and Research Institute of Life and Pharmaeutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea
2
Department of Internal Medicine, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea
3
Department of Pharmacology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea
4
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, 1666 Yeongsan-ro, muan, Jeonnam 58554, Korea
5
College of Pharmacy, Chosun University, 309 Philmun-daero, Dong-gu, Gwangju 61452, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2612; https://doi.org/10.3390/ijms20112612
Received: 16 April 2019 / Revised: 24 May 2019 / Accepted: 24 May 2019 / Published: 28 May 2019
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. View Full-Text
Keywords: deoxypodophyllotoxin; tubulin polymerization; apoptosis; mitotic arrest; tumorigenic potentials; colorectal cancer deoxypodophyllotoxin; tubulin polymerization; apoptosis; mitotic arrest; tumorigenic potentials; colorectal cancer
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Gamage, C.D.B.; Park, S.-Y.; Yang, Y.; Zhou, R.; Taş, İ.; Bae, W.K.; Kim, K.K.; Shim, J.-H.; Kim, E.; Yoon, G.; Kim, H. Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis. Int. J. Mol. Sci. 2019, 20, 2612.

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