Abstract

AbstractPancreatic and colorectal cancer are two of the most lethal cancers; this stems from poor prognosis. Current treatments may lack effectiveness and produce dangerous side effects, hence a need for alternatives. Medicinal plants like Millettia griffoniana may possess anti-cancer properties. This study aimed to isolate and identify compounds from M. griffoniana to test for potential anti-cancer activity on pancreatic and colorectal cancer. Seeds and root bark of M. griffoniana underwent solvent extraction and separation using column chromatography. Isolated compounds were screened using AlamarBlue assays and cytotoxic compounds were identified with 2D NMR. Compounds were subject to cellular viability assays using AlamarBlue and xCELLigence analysis. The Caspase Glo®-3/7 kit measured caspase activity and Real-Time PCR analysis measured apoptosis-related gene expression. 7 compounds were isolated and screened. Compounds 5 and 7 were chosen; identified as durmillone and isojamaicin. Both showed varying concentration-dependent cytotoxic activity, in AlamarBlue and xCELLigence assays, for both cell lines. Caspases 3 and 7 were up-regulated and both compounds up-regulated BAX and down-regulated BCL-2 and p53 in both cell lines. Durmillone and isojamaicin displayed cytotoxic activity on pancreatic and colorectal cancer. Apoptotic activity induced by the compounds was verified by the up-regulation of caspase activity and BAX and down-regulation of BCL-2 and p53. Further studies need to be done towards understanding the mechanisms by which these compounds bring about their cytotoxic activity.

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