As a part of a continuing study to elaborate the biological potency of globospiramine, investigations directed towards its anti-cancer activity were undertaken. Cell viability assays versus leukemia, Hela, HUVEC, breast (type T47D and MDA-MB-231) and prostate cancer cell lines were carried out using MTT and SRB methods. Globospiramine was observed to be cytotoxic on these cell-lines at very low microgram/mL or micromolar concentration ranges implicating promising anti-cancer properties (HUVEC GI50 = 5.4 �g/mL; K-562 GI50=1.4 �g/mL; HeLa CC50 =6.1 �g/mL; T47D IC50=1.11 �M; MDA-MB-231 IC50=1.17 �M; PC-3 IC50=1.77 �M). Reporter assay was performed on T47D cells lines transfected with pHRE-luc plasmid. While globospiramine had no effect on HIF activity at low concentrations, it had a significant inhibitory effect at concentrations greater than 5 mM under both chemical and physical hypoxia.  In the mitochondrial respiration assay, globospiramine showed increased mitochondrial respiration rate slightly at 0.1 mM indicating little mitochondrial uncoupling activity. In the anti-tubulin polymerization assay, globospiramine was observed to be cytotoxicp, but appeared to have a very different mechanism of action as compared to the known anticancer bisindole alkaloids, vinblastine and vincristine.

Biological assessment of the anticancer bisindole alkaloid globospiramine

245th National Meeting (2013)

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