We have earlier reported the in-vitro cytotoxic effect of the methanol extract of Cajanus cajan (L.) Millsp. (Leguminosae) and three of its constituents on some solid tumour cell lines.1 Pinostrobin, one of these constituents, is now reported to show significant inhibition in a cell proliferation assay using human CCRF-CEM leukaemia cells. The IC50 value obtained in an XTT assay was 5.0µM. Additionally, the compound was tested against the multi-drug resistant subline, CEM/ADR5000, where we observed a cross-resistance with the MDR cells. It arrested the migration of cells into the G1 phase of the cell cycle which could be demonstrated in a flow cytometry study. The compound also generated reactive oxygen species (ROS) in the ROS assay. The damage of the mitochondria membrane has been known to play a key role in apoptosis, hence we measured the effect of pinostrobin on its membrane potential (ΔΨm): it was intact. We further confirmed the mechanism behind the observed massive apoptosis by measuring its impact on the Fas receptors (Apo 1 or CD95), an important molecule of the extrinsic pathway of apoptosis. There was significant dose-dependent upregulation of the Fas receptors which explained the observed apoptosis. Significant accumulation of the compound in the cytosol after 2h incubation when assessed by auto-fluorescence assay was also found. Our findings lend support to the local use of C. cajan in prevention and therapy of cancer. An in-vivo study of pinostrobin in leukaemia subjects is suggested.
Acknowledgements: JSA thanks the Commonwealth Scholarship Commission and King's College London, United Kingdom for their financial support.
Reference: 1. Ashidi J.S. et al. (2006), Planta Med. 72:P016.
