Ginger Phytochemicals Exhibit Synergy to Inhibit Prostate Cancer Cell Proliferation

• Type of Material: Article
• Authors: Meera Brahmbhatt, Georgia State University; Sushma R. Gundala, Georgia State University; Ghazia Asif, Emory University; Shahab A Shamsi, Georgia State University; Ritu Aneja, Georgia State University
• Language: English
• Date: 2013-02-01
• Publisher: Taylor & Francis (Routledge): STM, Behavioural Science and Public Health Titles
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Taylor and Francis Group, LLC.
• Final Published Version (URL): http://dx.doi.org/10.1080/01635581.2013.749925
• Title of Journal or Parent Work: Nutrition and Cancer
• ISSN: 0163-5581
• Volume: 65
• Issue: 2
• Start Page: 263
• End Page: 272
• Grant/Funding Information: This work was supported by grants to RA from the National Cancer Institute at the National Institutes of Health (1R00CA131489).
• Keywords: 6-GINGEROL; CONSTITUENTS; Life Sciences & Biomedicine; LUNG-CANCER; APOPTOSIS; Science & Technology; Nutrition & Dietetics; ELLAGIC ACID; ANTIOXIDANT; EXTRACT; Oncology; COMBINATION; CHEMOPREVENTION; VEGETABLES
• Research Categories: Chemistry, General; Health Sciences, Oncology; Biology, Genetics

Abstract

Dietary phytochemicals offer nontoxic therapeutic management as well as chemopreventive intervention for slow-growing prostate cancers. However, the limited success of several single-agent clinical trials suggest a paradigm shift that the health benefits of fruits and vegetables are not ascribable to individual phytochemicals, rather may be ascribed to synergistic interactions among them. We recently reported growth-inhibiting and apoptosis-inducing properties of ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogoal, remains elusive. Here we show antiproliferative efficacy of the most-active GE biophenolics as single-agents and in binary combinations, and investigate the nature of their interactions using the Chou-Talalay combination index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit proliferation of PC-3 cells with CI values ranging from 0.03 to 0.88. To appreciate synergy among phytochemicals present in GE, the natural abundance of ginger biophenolics was quantitated using LC-UV/MS. Interestingly, combining GE with its constituents (in particular, 6-gingerol) resulted in significant augmentation of GE's antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management.