Abstract
Murraya koenigii (Rutaceae), a tropical to the sub-tropical tree is well disseminated in the eastern region of India and known for its curative potential against ample diseases and disorders. In this study, the methanolic extract of Murraya koenigii seeds (MEMS) was screened for the first time to determine the in vitro cytotoxicity and caspase-mediated apoptosis-inducing effects against breast and colon cancer cells. Both in vitro assay and in silico molecular docking study were performed to screen the anti-proliferative potential of MEMS. Cicer arietinum seeds germination and Allium cepa root tip inhibition assay were used to study the anti-mitotic effect of the MEMS. Angiogenesis inhibition and cytotoxicity of MEMS were determined using chicken egg chorioallantoic membrane (CAM) assay and brine shrimp lethality bioassay respectively. MTT assay was used to exhibit the cell viability while apoptotic cells were determined using annexin V-fluorescein isothiocyanate assay. The activity of caspase-3 and caspase-7 was performed using the luminometric assay. SeDeM diagram and Heckel plot were generated for MEMS to predict their compression suitability. The MEMS significantly reduced the growth of Cicer arietinum seeds sprout (P<0.05) compared to control and on a par with methotrexate treated groups. Cell division in Allium cepa roots was diminished by 7.73 fold compared to control at the dose of 1000 µg/mL. MEMS showed moderate anti-angiogenic activity (14.81%) on CAM and considerable cytotoxicity (LD50= 40.860 μg/mL) to brine shrimps. MEMS elicited the prominent cytotoxic effect against DLD-1 colorectal cancer cells compared to MCF-7 breast cancer cells. It showed caspase-mediated apoptosis with reduced mitochondrial membrane potential. Early and late apoptotic rates were observed to be 7.13 and 2.57 fold higher respectively, than control. In silico docking analysis corroborated that neplanocin A and girinimbine interacted with proteolytic enzymes (caspase-3 and caspase-7) mainly by hydrogen bonding, aromatic, hydrophobic, and Van der Waals interactions. SeDeM diagram and Heckel plot revealed the poor compression behavior of MEMS. However, MEMS is having enormous potential and can be processed for further in vivo experiments.
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