SEMINAR ANNOUNCEMENT

PhD Thesis Defence Seminar
Investigation of the cytotoxic and apoptotic effects induced by arsenics in gynecological cancer cells

by

Ms Yuhong
Department of Pharmacy
National University of Singapore

on

Date: Friday, 04 July2003
Time: 1100 - 1200 hrs
Venue: S4-05-10

Synopsis:

Arsenic trioxide (As2O3) has been shown clinically effective in the treatment of acute promyelocytic leukemia, however, little is known about the potential use of arsenic compounds in the treatment of human ovarian cancer. In this thesis, we investigated the cytotoxic and apoptotic effect of arsenic compounds, As2O3 or As2S3, in human ovarian and cervical cancer cells. Our results showed that at clinically achievable concentrations, As2O3 or As2S3 could selectively induce cytotoxicity and apoptosis effect in both cisplatin-sensitive and -resistant human ovarian and cervical cancer cells while with little effect to normal cells. The sensitivity of these cancer cells to arsenics was independent of the functional p53 status. Bcl-2 protein was down-regulated in the arsenic-sensitive cancer cells, while bax protein was almost no change. Caspase-3 activation might not be essential in the arsenic-induced apoptosis. We also demonstrated that the sensitivity of these cancer cells to arsenics might be inversely correlated with the intracellular GSH levels, which is known to affect the activity of arsenicals. Depleting GSH contents with buthionine sulfoximine (BSO) could sensitize cancer cells to As2O3 or As2S3, even in the arsenic-resistant cells. Our results indicate that As2O3 or As2S3 might be promising agents in the treatment of human ovarian and cervical caners, especially in the cispaltin-resistant patients.

Key Words: As2O3; As2S3; Apoptosis; p53 protein; bcl-2 protein; GSH (glutathione).

ALL ARE WELCOME