Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L.) Millsp.] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway.

Abstract

Cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) is an isoflavanone from Pigeonpea [Cajanus cajan (L.) Millsp.] roots. As the most effective phytoalexin in pigeonpea, the cytotoxic activity of cajanol towards cancer cells has not been report as yet. In the present study, the anticancer activity of cajanol towards MCF-7 human breast cancer cells was investigated. In order to explore the underlying mechanism of cell growth inhibition of cajanol, cell cycle distribution, DNA fragmentation assay and morphological assessment of nuclear change, ROS generation, mitochondrial membrane potential (DeltaPsim) disruption, and expression of caspase-3 and caspase-9, Bax, Bcl-2, PARP and cytochrome c were measured in MCF-7 cells. Cajanol inhibited the growth of MCF-7 cells in a time and dose-dependent manner. The IC(50) value was 54.05 microM after 72 h treatment, 58.32 microM after 48 h; and 83.42 microM after 24h. Cajanol arrested the cell cycle in the G2/M phase and induced apoptosis via a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that cajanol inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage. All of these signal transduction pathways are involved in initiating apoptosis. To the best of our knowledge, this is the first report demonstrating the cytotoxic activity of cajanol towards cancer cells in vitro.

• Authors: Meng Luo, Xia Liu, Yuangang Zu, Yujie Fu, Su Zhang, Liping Yao, Thomas Efferth
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 188 Issue 1 Pg. 151-60 (Oct 06 2010) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 20638373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Isoflavones
• Reactive Oxygen Species
• cajanol

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (enzymology, metabolism, pathology)
• Cajanus (chemistry)
• Cell Line, Tumor
• Female
• Flow Cytometry
• Humans
• Isoflavones (pharmacology)
• Mitochondria (drug effects, metabolism)
• Plant Roots (chemistry)
• Reactive Oxygen Species (metabolism)