A new protoapigenone analog RY10-4 induces apoptosis and suppresses invasion through the PI3K/Akt pathway in human breast cancer.

Abstract

RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against a broad spectrum of human cancer cells. Here we investigate its anti-tumor activity on breast cancer. The results indicated that RY10-4 suppressed proliferation, arrested cell cycle, induced apoptosis and inhibited invasion in MDA-MB-231, MCF-7 and SKBR3 breast cancer cells. Western blot analysis showed that RY10-4 down-regulated the PI3K/Akt signaling pathway and inhibited doxorubicin-induced p-Akt. Moreover, it effectively suppressed tumor growth in mice without major side effects. Therefore, RY10-4 had potential anti-tumor activity, and could be used as a lead to design more potent derivatives.

• Authors: Qianying Yuan, Shaoxin Cai, Xuenong Zhang, Ziwei Liu, Zhaoming Li, Xuelai Luo, Chaomei Xiong, Jianping Wang, Junbo Hu, Jinlan Ruan
• Journal: Cancer letters (Cancer Lett) Vol. 324 Issue 2 Pg. 210-20 (Nov 28 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22652174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one
• Antineoplastic Agents
• Pyrones
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyrones (pharmacology)
• S Phase Cell Cycle Checkpoints (drug effects)
• Signal Transduction (drug effects)
• Time Factors
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays