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BioMed Research International
Volume 2015, Article ID 649263, 12 pages
http://dx.doi.org/10.1155/2015/649263
Research Article

Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio

1Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA
2Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa 516003, India
3Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA
4The Pennsylvania State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA

Received 23 March 2015; Revised 22 May 2015; Accepted 30 May 2015

Academic Editor: Xin-yuan Guan

Copyright © 2015 Ramakrishna Vadde et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs) have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs). The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS) of methanol extract of triphala (MET) were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo.