Abstract
Plant derived products have steadily gained momentum in treatment of cancer over the past decades. Curcuma and its derivatives, in particular, have diverse medicinal properties including anticancer potential with proven safety as supported by numerous in vivo and in vitro studies. A defective Mis-Match Repair (MMR) is implicated in solid tumors but its role in haematologic malignancies is not keenly studied and the current literature suggests that it is limited. Nonetheless, there are multiple pathways interjecting the mismatch repair proteins in haematologic cancers that may have a direct or indirect implication in progression of the disease. Here, through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L. and Curcuma caesia Roxb.) which in turn, profoundly controls MMR protein function. These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and thus revive the MMR function preventing genomic instability. These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways.
Highlights
Plant derived products have steadily gained momentum in treatment of cancer over the past decades
Mutations in MisMatch Repair (MMR) genes viz. MSH2 and MLH1 and promoter hypermethylation of MLH1 correlates with loss of function of mismatch repair and acute myeloid leukaemia (AML) (Acute Myeloid Leukaemia) pathogenesis[6]
For over three decades plant products have secured a place in cancer treatment and these natural products have certainly come a long way as anticancer drugs
Summary
Plant derived products have steadily gained momentum in treatment of cancer over the past decades. Through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L. and Curcuma caesia Roxb.) which in turn, profoundly controls MMR protein function These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and revive the MMR function preventing genomic instability These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways. The anticancer mechanism of curcumin involves inhibition of proliferation, invasion, and metastasis, and induction of apoptosis which works via modulating various signaling pathways[13,14]
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