Cantharidin induces DNA damage and inhibits DNA repair-associated protein levels in NCI-H460 human lung cancer cells.

Abstract

Cantharidin is one of the major compounds from mylabris and it has cytotoxic effects in many different types of human cancer cells. Previously, we found that cantharidin induced cell death through cell cycle arrest and apoptosis induction in human lung cancer NCI-H460 cells. However, cantharidin-affected DNA damage, repair, and associated protein levels in NCI-H460 cells have not been examined. In this study, we determined whether cantharidin induced DNA damage and condensation and altered levels of proteins in NCI-H460 cells in vitro. Incubation of NCI-H460 cells with 0, 2.5, 5, 10, and 15 μM of cantharidin caused a longer DNA migration smear (comet tail). Cantharidin also increased DNA condensation. These effects were dose-dependent. Cantharidin (5, 10, and 15 μM) treatment of NCI-H460 cells reduced protein levels of ataxia telangiectasia mutated (ATM), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O(6) -methylguanine-DNA methyltransferase (MGMT), and mediator of DNA damage checkpoint protein 1 (MDC1). Protein translocation of p-p53, p-H2A.X (S140), and MDC1 from cytoplasm to nucleus was induced by cantharidin in NCI-H460 cells. Taken together, this study showed that cantharidin caused DNA damage and inhibited levels of DNA repair-associated proteins. These effects may contribute to cantharidin-induced cell death in vitro.

• Authors: Te-Chun Hsia, Ju-Hwa Lin, Shu-Chun Hsu, Nou-Ying Tang, Hsu-Feng Lu, Shin-Hwar Wu, Jaung-Geng Lin, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 30 Issue 10 Pg. 1135-43 (Sep 2015) ISSN: 1522-7278 [Electronic] United States
• PMID: 24639390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• DNA Repair Enzymes
• Cantharidin

Topics

• Apoptosis (drug effects)
• Cantharidin (toxicity)
• Cell Line, Tumor
• Comet Assay
• DNA Damage (drug effects)
• DNA Repair (drug effects)
• DNA Repair Enzymes (antagonists & inhibitors, metabolism)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Microscopy, Confocal