Abstract 1249: Procyanidin B2-3,3′-di-O-gallate targets cancer cell metabolism in its efficacy against human prostate carcinoma cells
Authors: Agarwal Chapla , Kumar Dileep , Tyagi Alpna , Serkova Natalie , Wempe Michael , Raina Komal , Agarwal Rajesh 
Published: July 2017

Abstract
The metabolic profile of various cancerous tissues can be correlated with cell growth and death, specific tumor type as well as the pathological stage of tumor. In recent times, prostatic tissue metabolomics using spectroscopy methods has helped to identify and establish the metabolic profiles specific to prostate cancer (PCa) malignancy. Thus, the evaluation of the anticancer efficacy of an agent can be considered incomplete without assessing its effect on the metabolic profile of the tumor tissue. With this rationale, herein, we carried out a metabolomics study on human PCa cell lines after procyanidin B2-3,3′-di-O-gallate (B2G2) exposure, which was recently identified by us as most effective agent in grape seed extract for growth inhibition and apoptotic death of human PCa cells. Specifically, we employed quantitative high-resolution nuclear magnetic resonance spectroscopy (1H-, 13C- and 31P-NMR) to assess the metabolic profile and energy state of the B2G2-treated human PCa cell lines PC3 and C42B. This approach helped us assess global metabolic profile, including glucose metabolism, energy state, and lipid metabolism in these cells after B2G2 treatment. We also studied the time-course (4-72 hrs) of B2G2 effect on glucose uptake and lactate release in the media of B2G2-treated PCa cells. Our results indicated that there was differential effect of B2G2 on mitochondrial glucose metabolism in these cells. While glucose uptake was markedly reduced as a function of time, there was also a significant decrease in extracellular lactate export with increased B2G2 exposure-time. Importantly, B2G2 preserved citrate concentration in the PCa cells as indicated by an increase in citrate levels after treatments; citrate generation is indicative of normal secretion functions of the prostate epithelial cells. The fact that the citrate was not further utilized for cholesterol synthesis was also confirmed by a decrease in cholesterol levels in these cells, indicating decreased cholesterogenesis by B2G2. Together, these results suggest that B2G2 differentially induces metabolic alterations in various PCa cell lines, which could be associated with its effects on cell growth, proliferation and death, as well as androgen dependency (or lack of it). In in vivo study examining B2G2 effect on PCa PC3 tumor xenograft growth in athymic nu/nu mice, B2G2 treatment (dose: 5mg/kg body weight of mice; given daily as intraperitoneal injections) significantly decreased tumor volume and tumor weight by ∼61% and ∼52% (both P≤ 0.01), respectively, after 5 weeks of treatments. Taken together, these studies indicate anti-PCa efficacy of B2G2 under both in vitro and in vivo scenario and warrant further extensive studies to establish its efficacy in other PCa models.
Citation Format: Chapla Agarwal, Dileep Kumar, Alpna Tyagi, Natalie Serkova, Michael Wempe, Komal Raina, Rajesh Agarwal. Procyanidin B2-3,3′-di-O-gallate targets cancer cell metabolism in its efficacy against human prostate carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1249. doi:10.1158/1538-7445.AM2017-1249