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The study emphasizes the growth inhibitory effect of harmaline on HeLa (human cervical cancer) cell line and mode and mechanism of binding with CT DNA (calf thymus DNA). The results of cytotoxic study performed through MTT assay indicates that harmaline have concentration dependent growth inhibitory effect on HeLa cell line with GI50 value of 28 μM. Furthermore, the alkaloid induced DNA damage and changes in mitochondrial membrane potential in the cell line. The alkaloid shows reactive oxygen species dependent cellular damage with significant arrest in G2/M population of the cell. Biophysical experiments further established the Kiw value (product of cooperative binding affinity and the cooperative factor) of harmaline with CT DNA to be 5.60 × 105 M−1. Harmaline showed a progressive quenching of the fluorescence emission spectra. Circular dichroism study shows significant structural changes of DNAwith subsequent induction of optical activity in the bound achiral alkaloid molecule. The alkaloid stabilizes the DNA to 10°C. Intercalated state of harmaline inside DNA helix was shown by viscometric and ferrocyanide quenching. The results highlight the importance of alkaloidDNA interaction for developing nucleic acid based therapeutic agents.

Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: Apoptotic induction and DNA interaction study