Regulating the expression of matrix metalloproteinases to inhibit ovarian carcinoma using isoquinoline alkaloid from Allium ascalonicum

Ovarian carcinoma is one of the fatal gynecological cancers due to the lack of clinical symptoms at earlier stages of disease leading to metastasis and lower survival rates. Hence, an in-depth exploration of the mechanisms of metastasis facilitates the development of novel-targeted therapeutic strategies to treat the disease. Research studies have reported that three predominant Matrix metalloproteinases (MMPs), namely, MMP14, MMP2 and MMP9 can induce the migration of ovarian cancer cells, Epithelial-Mesenchymal transition, breakdown of extracellular matrix, upregulation of expression of transcription factors etc. in the microenvironment of ovarian tumors. In our current research, these predominant MMPs were used as target proteins and docked with potential anti-cancerous phyto-nutraceuticals present in Allium ascalonicum species. Allium ascalonicum, commonly referred to as Shallots is being used in various cuisines worldwide and is still largely unexploited for its anti-cancer properties. Docking results, revealed three potential phyto-nutraceuticals, of which, 1-[[3,5-bis(phenylmethoxy)phenyl]methyl]-6-methoxy-2-methyl-3,4-dihydro-1H-isoquinoline, an isoquinoline alkaloid was considered the best, since it exhibits significant binding affinity when compared to that of the standard drug, Melphalan. Molecular dynamic simulation studies exhibited that MMP2 is highly flexible and can form more stable interactions. Furthermore, simulation studies of finest interaction pose of the target MMPs with the best phyto-nutraceutical, revealed stable interactions and occurrence of conformational changes. The results, also suggested that, the best phyto-nutraceutical of Allium ascalonicum is a novel isoquinoline alkaloid, with favorable bioavailability scores that interact with target MMPs to control the progression and metastasis of ovarian cancer, proposing the prospect of formulating it into sustainable medications for treating metastasized Ovarian Cancer.