Naphthazarin enhances ionizing radiation-induced cell cycle arrest and apoptosis in human breast cancer cells.

Abstract

Naphthazarin (Naph, DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is one of the naturally available 1,4-naphthoquinone derivatives that are well-known for their anti-inflammatory, antioxidant, antibacterial and antitumor cytotoxic effects in cancer cells. Herein, we investigated whether Naph has effects on cell cycle arrest and apoptosis in MCF-7 human breast cancer cells exposed to ionizing radiation (IR). Naph reduced the MCF-7 cell viability in a dose-dependent manner. We also found that Naph and/or IR increased the p53-dependent p21 (CIP/WAF1) promoter activity. Noteworthy, our ChIP assay results showed that Naph and IR combined treatment activated the p21 promoter via inhibition of binding of multi-domain proteins, DNMT1, UHRF1 and HDAC1. Apoptosis and cell cycle analyses demonstrated that Naph and IR combined treatment induced cell cycle arrest and apoptosis in MCF-7 cells. Herein, we showed that Naph treatment enhances IR-induced cell cycle arrest and death in MCF-7 human breast cancer cells through the p53-dependent p21 activation mechanism. These results suggest that Naph might sensitize breast cancer cells to radiotherapy by enhancing the p53-p21 mechanism activity.

• Authors: Min Young Kim, Seong-Joon Park, Jae Woong Shim, Kwangmo Yang, Ho Sung Kang, Kyu Heo
• Journal: International journal of oncology (Int J Oncol) Vol. 46 Issue 4 Pg. 1659-66 (Apr 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25633658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Naphthoquinones
• Radiation-Sensitizing Agents
• naphthazarin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Breast Neoplasms (drug therapy, genetics, radiotherapy)
• Cell Cycle Checkpoints (drug effects, radiation effects)
• Cell Proliferation (drug effects, radiation effects)
• Chemoradiotherapy (methods)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Dose-Response Relationship, Drug
• Female
• Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
• Humans
• MCF-7 Cells
• Naphthoquinones (pharmacology)
• Promoter Regions, Genetic (drug effects, radiation effects)
• Radiation-Sensitizing Agents (pharmacology)