Abstract 4627: Potent chemotherapeutic activity of green tea polyphenols, blueberry anthocyanidin mixture and cisplatin: Synergistic effects

Abstract

Abstract A significant progress has been made in the prognosis of several cancers (e.g., breast and prostate cancers). However, the prognosis of lung cancer remains grim. Furthermore, up to 50% of stage I/II non-small-cell lung cancer (NSCLC) patients develop recurrence/metastasis within five years of their treatments. It is eminent that natural compounds or food-based bioactives with minimal toxicity be identified for their use in neo-adjuvant chemotherapy and/or after the primary cancer treatment for enhanced efficacy. Green tea and berries are drawing increased attention due to their potential anti-cancer effects. The active compounds in green tea and berries are polyphenols, e.g., epigallocatechin gallate (EGCG) and anthocyanidins (e.g. delphinidin, cyanidin, peonidin, petunidin, malvidin in blueberry), respectively. We previously demonstrated synergistic antiproliferative activity from these Anths against H1299 lung cancer cells both in vitro and in vivo (Kausar et al. AACR 51: 1884, 2010). In this study we investigated the combined effect of EGCG and the blueberry anthocyanidins (EGCG-Anths) alone and in combination with a common chemotherapeutic drug, cisplatin on lung cancer H1299 cell using MTT assay. The antiproliferative activity of EGCG-Anths (6 μM), measured as IC50, was found to be 2- and 4-fold lower compared with Anths (12 μM) and EGCG (21 μM) alone, respectively. The IC50 of cisplatin was found to be ≈50 μM. However, when combined with the EGCG-Anths (10 μM each), the IC50 of cisplatin was significantly reduced (<3 μM). Flow cytometric analysis for cell cycle distribution and apoptosis revealed cell cycle arrest and enhanced apotosis induced by the combination mixture. Western blot analysis for the involved molecular targets showed that selected proteins (cyclin D1, B1, Cdc2, p21, PCNA, Bax, Bcl-2, PARP, etc.) associated with cell cycle and apoptosis were more significantly modulated by the combination, EGCG-Anths-cisplatin than with the individual entities. Together, our data suggest that combination of EGCG-Anths alone or in combination with suboptimal doses of cisplatin may be effective in neo-adjuvant chemotherapy or can be used as maintenance drug for the prevention of lung cancer recurrence/metastasis and minimize toxicity issues associated with high dose cisplatin (Supported from KLCRP, T32-ES011564 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4627. doi:10.1158/1538-7445.AM2011-4627