Presenter: Kathy Qian Luo, Associate Professor

University: Nanyang Technological University, Singapore

Time: 10:30-11:30, December 21, 2011

Venue: Room 101, North Building, Zhongguancun, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Cancer is a deadly disease which kills over 7 million people each year around the world. In recent years, it has been recognized that the occurrence of cancer is not only a result of uncontrolled cell proliferation, but is also closely related to cancer cells resistant to apoptosis, a programmed death process used by our body to remove unwanted cells. Thus, a new approach of treating cancer is to re-activate apoptosis in cancer cells using apoptosis-inducing compounds.

To find such agents, a sensitive high-throughput assay for detecting apoptosis is needed to speed up the searching process. Unfortunately, the existing apoptotic assays are designed for in vitro detection of apoptosis and not suitable for high throughput drug discovery. Recently, we have developed a novel fluorescence resonance energy transfer (FRET)-based biosensor that can detect the most important event in apoptosis: caspase-3 activation, in living cells.

This novel method, in conjunction with cell-based bioassays and animal experiments, were used to identify new anti-cancer compounds from Chinese herbal medicines. After screening over 300 herbal samples, several promising candidates have been identified. In particular, tanshinone TIIA (TIIA) from Danshen (丹参) was found to kill cancer cells very effectively. In order to further improve its water solubility as well as cancer efficacy, the chemical structure of TIIA was modified to generate a novel compound, acetyltanshinone (ATA). ATA displayed much higher cytotoxicity against human breast cancer cells than non-cancerous breast cells, and could significantly inhibit the growth of human tumor xenograft, without affecting the body weight of the mouse. Mechanistic studies indicate that this agent kills cancer cells by generating reactive oxygen species to activate Bax-mediated cell death process.