Pharmaceutical Research & Development (Track)

STUDIES ON COMBINATIONS OF TARGETED DRUGS WITH PLANT-DERIVED COMPOUNDS IN COLORECTAL CANCER

Hana Faisal Bali, Jun Qing Yu, Philip Beale, Charles Chan and Fazlul Huq

Discipline of Biomedical Science, University of Sydney, Rhodes, Australia

Abstract

Introduction: Colorectal cancer is the second most common cancer affecting people in Australia for which the intrinsic drug resistance presents as a major problem. Because mechanisms of action of tumour active phytochemicals are different from those of targeted drugs, it is logical to think that their combinations may produce synergistic outcomes dependent on sequence of administration and concentration. This study aims to investigate changes in activity from combinations of platinum drugs with selected phytochemicals in colorectal tumour models.

Methods: Cytotoxic activities of compounds alone and in combination against colorectal cancer cell lines H29/129, Caco-2, LIM1215 and LIM2405 are determined using MTT reduction assay. Combination indices are used as a quantitative measure of nature of the combined drug action.

Results: IC₅₀ (µM) values of compounds against H29/129, Caco-2, LIM1215 and LIM2405 are given in the following table.

Drug	IC50 values (µM) in human colorectal cancer cell lines
	H29/129	Caco-2	LIM1215	LIM2405
Cisplatin	5.00	26.02	12.67	4.99
Oxaliplatin	0.47	2.72	9.47	7.62
Curcumin	0.86	1.06	31.30	8.34
EGCG	28.40	61.30	14.61	37.01
6-gingerol	146.46	116.96	147.39	161.89
Colchicine	0.025	0.007	0.016	0.01

 

Studies on drug combination are in progress. The results thus far indicate that combinations of oxaliplatin with curcumin and EGCG are synergistic in Caco-2, H29/219 and LIM1215 cell lines but additive in LIM 2405 colorectal cancer cell line.