Resveratrol analog, N-(4-methoxyphenyl)-3,5-dimethoxybenzamide induces G2/M phase cell cycle arrest and apoptosis in HeLa human cervical cancer cells.

Abstract

In this study, several resveratrol analogs were synthesized and evaluated in search of a more effective anti-proliferative resveratrol analog. Among the evaluated resveratrol analogs, we have identified N-(4-methoxyphenyl)-3,5-dimethoxybenamide (MPDB) as a potent anti-proliferative compound. Treatment with MPDB resulted in G2/M phase cell cycle arrest, which was accompanied by alteration of G2/M-related protein expression and phosphorylation. MPDB-induced G2/M arrest was blocked by transfection of ATM/ATR siRNAs, indicating the critical role of ATM/ATR in G2/M phase arrest. In addition, treatment with MPDB displayed the activation of caspase and decreased Bcl-xl protein expression after 20 h in HeLa cells. Moreover, MPDB increased cytosolic cytochrome c release and Fas and Fas-L protein expression, indicating intrinsic and extrinsic apoptosis pathway, respectively. These results suggest that MPDB is a new and potent compound that induces ATM/ATR-dependent G2/M phase cell cycle arrest and apoptosis, implicating it as a putative candidate in the investment of cervical cancer therapy.

• Authors: Kyung-Won Lee, Kyung-Sook Chung, Jeong-Hun Lee, Jung-Hye Choi, Sang Yoon Choi, Sanghee Kim, Jae Yeol Lee, Kyung-Tae Lee
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 124 Pg. 101-111 (Feb 2019) ISSN: 1873-6351 [Electronic] England
• PMID: 30508562 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• BCL2L1 protein, human
• Benzamides
• bcl-X Protein
• Checkpoint Kinase 2
• ATM protein, human
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins
• CHEK1 protein, human
• CHEK2 protein, human
• Checkpoint Kinase 1
• CDC2 Protein Kinase
• CDK1 protein, human

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Benzamides (pharmacology)
• CDC2 Protein Kinase (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Checkpoint Kinase 1 (metabolism)
• Checkpoint Kinase 2 (metabolism)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Phosphorylation
• Signal Transduction (drug effects)
• Uterine Cervical Neoplasms (drug therapy)
• bcl-X Protein (metabolism)