Fazlul Huq


School of Medical Sciences, The University of Sydney, Australia

Abstract:

Although much progress has been made in cancer treatment and therapy, it still remains as one of the most dreaded diseases of our time. Cancer is not a single; currently more than two hundred diseases all with the common characteristic of metastasis are termed cancer.

Cancer sufferers often use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In our continued study we have been investigating synergism from the combination of platinum and other metal-based drugs and a number of tumour active phytochemicals including paclitaxel, colchicine, curcumin, epigallocatechin-3-gallate, chlorophyllin, andrographolide, thymoquinone, resveratrol, betulinic acid, uursolic acid, oleanolic acid and artemisinin in a number of human humour models as a function of concentration and the sequence of administration. Both the dose effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals show concentration- and sequence-dependent synergism in cell lines. Generally the degree of synergism is found to be greater in sequenced administration such as 0/2 h, 2/0 h, 0/4 h and 4/0 h than the bolus. The variation in the nature of the combined drug action from being highly synergistic to antagonistic with the change in sequence of administration clearly indicates that the action of one drug modulates that of the other (towards the induction or inhibition of apoptosis). Proteomic studies to identify the key proteins associated with platinum resistance are on-going. Based on preliminry results we have identified five proteins namely TCTP, RSSA Human, MARE1_HUMAN, ANXA5, ATPB, that are believed to be associated with platinum resistance in ovarian cancer cell line A2780^cisR. Synergistic combination of CS and Tax is found to restore expressions of TCTP and ATPB, that of CS and Col is found to restore expressions of ANXA5 and ATPB, and that of CS and Egcg is found to restore expressions of TCTP and ANXA5. Changes in antioxidant status is also determined. In this presentation, I will be reporting on the lastest findings.