Bitter melon extract inhibits proliferation of Trypanosoma brucei bloodstream forms in vitro

Trypanosoma brucei is the causative agent of sleeping sickness, a fatal disease prevalent in sub-Saharan Africa. The few currently available drug treatments are dated and face problems with toxicity and resistance. For these reasons, there is an urgent need for the development of new chemotherapies for the treatment of sleeping sickness. In this study, we investigated the trypanocidal activity of bitter melon extract. Recently, it has been shown that bitter melon extracts display cytotoxic activity towards different cancer cell lines. However, agents exhibiting anti-tumour activity are usually also inhibiting the growth of T. brucei. Treatment of bloodstream forms of T. brucei with extracts prepared from Chinese and Indian bitter melon varieties resulted in a decrease in cell proliferation. In contrast, human myeloid leukaemia HL-60 cells were 3-6 times less sensitive to the extracts than trypanosomes. Initial fractionation of bitter melon extracts indicated that the trypanocidal activity of the extract is associated with at least two different classes of substances: one class of larger molecular weight compounds (>3 kDa) causing rapid lysis of trypanosomes and one class of smaller molecular weight compounds (<3 kDa) inducing accumulation of the parasites in the G(2)-M phase of the cell cycle. Together, the results suggest that bitter melon is a promising source for trypanocidal agents which could be used as lead compounds for the development of novel anti-sleeping sickness drugs.