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

Abstract

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.

• Authors: Chathurika D B Gamage, So-Yeon Park, Yi Yang, Rui Zhou, İsa Taş, Woo Kyun Bae, Kyung Keun Kim, Jung-Hyun Shim, Eunae Kim, Goo Yoon, Hangun Kim
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 11 (May 28 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31141929 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Drugs, Chinese Herbal
• Tubulin Modulators
• deoxypodophyllotoxin
• Podophyllotoxin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Caco-2 Cells
• Carcinogenesis (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Drugs, Chinese Herbal
• HT29 Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Microtubules (drug effects, metabolism)
• Podophyllotoxin (analogs & derivatives, pharmacology, therapeutic use)
• Tubulin Modulators (pharmacology, therapeutic use)