γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Acacia nilotica is widely distributed in Asia. In India, it occupies an important place in the indigenous system of medicine against anti-inflammatory, antioxidant, cancers, and/or tumors.

AIM OF THE STUDY:

The purpose of this study is to investigate the inhibitory effect of Acacia nilotica leaves extract and γ-Sitosterol on cell proliferation, the apoptotic effect and cell cycle arrest in breast and lung cancer cells.

MATERIALS AND METHODS:

GC-MS and HPLC were used to determine the chemical constituents of this extract and γ-Sitosterol respectively. Human MCF-7 and A549 cell lines were treated with Acacia nilotica extract and γ-Sitosterol. Cell viability was determined by MTT assay. Cell proliferation was determined by BrdU incorporation assay. Apoptosis was detected by cell morphologic observation through AO/EtBr staining, cell cycle analysis, and immunoblot analysis on the expression of protein associated with cell cycle arrest.

RESULTS:

Experimental results of bioactive compound analysis indicate that γ-Sitosterol, bioactive ingredients of Acacia nilotica extract. The IC(50) value of extract on MCF-7 and A549 cancer cells was 493.3±15.2 and 696.6±11.5 μg/ml, respectively. Acacia nilotica extract and γ-Sitosterol were inhibited the cell proliferation by 54.34±1.8 and 42.18±3.9% for MCF-7 and 58.26±1.5 and 44.36±3.05% for A549 cells. The percentage of apoptotic cells observed in the MCF-7 and A549 cell lines were increased to 42.46 and 36.8% of extract; 46.68 and 43.24% for γ-Sitosterol respectively. Flow cytometric analysis results demonstrate that cells were arrested at the G2/M phase and decrease the c-Myc expression.

CONCLUSIONS:

This study demonstrates in vitro results, which support the ethnomedical use of γ-Sitosterol against cancer. Experimental results of this study suggest that γ-Sitosterol exerts potential anticancer activity through the growth inhibition, cell cycle arrest and the apoptosis on cancer cells.

• Authors: Shenbagamoorthy Sundarraj, Ramar Thangam, Vellingiri Sreevani, Krishnasamy Kaveri, Palani Gunasekaran, Shanmugam Achiraman, Soundarapandian Kannan
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 141 Issue 3 Pg. 803-9 (Jun 14 2012) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 22440953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclin B
• Cyclin E
• Plant Extracts
• Proto-Oncogene Proteins c-myc
• Sitosterols
• gamma-sitosterol

Topics

• Acacia
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin B (metabolism)
• Cyclin E (metabolism)
• Humans
• Plant Extracts (chemistry, pharmacology)
• Plant Leaves
• Proto-Oncogene Proteins c-myc (metabolism)
• Sitosterols (isolation & purification, pharmacology)