Does Theobromine Increase the Apoptotic Effect of STI571?

Abstract

Objective: STI571, a selective tyrosine kinase inhibitor is used in CML chemotherapy. It has limited effects in some cases due to drug resistance and intoxication as other chemotherapeutic agents. Thus, many cancer patients use dietary supplements and herbal extracts for increasing the effectiveness of chemotherapeutic agents. Theobromine, a metabolite of cacao has prooxidant effects and regulates intercellular signaling pathways. The aim of the study is to determine the potential apoptotic effects of STI571 and theobromine on K562 cells, when used alone and in combination.

Methods: Inhibitory concentrations of STI571 and theobromine were determined by MTT method. Both agents were applied to the cells at 48 h time period alone and in combination. Caspase activities were assessed colorimetrically. Apoptosis and necrosis were evaluated by using acridine orange/ethidium bromide staining. p<0.05 was considered as statistically significant.

Results: Caspase activities increased when both agents administrated alone. Theobromine increased effects of STI571 on caspase activities in time and type dependent manner (p<0.05). Apoptotic cell rates also increased when two agents applied in combination (p<0.05) in time dependent manner. Theobromine also reduced necrotic cell rates.

Conclusion: Although there are limited data about the intracellular effects of theobromine, we showed that theobromine has effects on the caspase pathway related apoptotic response carried out by STI571. We believe that this in vitro study will shed light for further researches.