Abstract
Abstract Zoledronic Acid (ZA) is a potent nitrogen-containing bisphosphonates (NBP) has been extensively used to limit bone turnover in a various diseases including tumors. Recently, clinical trails of Zoledronic Acid demonstrated direct anti-cancer effects as well as the known skeletal-related events. We investigated the effect of 4 NBPs on human tumor cells proliferation and found ZA is most potent for GBM cell, breast cell and GBM patients' stem-cell-like cells. ZA also effectively inhibited GBM tumor growth in mouse model. ZA stimulated strong autophagy but not apoptotic signals in all tested cells. One intermediate product of cholesterols synthesis pathway—-geranylgeranyl diphosphate (GGPP) rescued cell from the cytotoxicity of ZA. Knock-down RABGGTA, which encoded a subunit of the Rab geranylgeranyltransferase proteins, induced a similar effect as Zoledronic Acid in cancer cell lines. These data suggested great potential for Zoledronic Acid against human cancer. Note: This abstract was not presented at the meeting. Citation Format: Pengfei Jiang, Rajesh Mukthavavam, Natsuko Nomura, Sandeep C. Pingle, Santosh Kesari. Direct anti-cancer effects of zoledronic acid on human cancer cell. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1628. doi:10.1158/1538-7445.AM2014-1628
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