Related Experiment Video
Updated: May 21, 2025
Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity
Published on: December 31, 2015
Regulating the expression of matrix metalloproteinases to inhibit ovarian carcinoma using isoquinoline alkaloid from
Karunya Jenin Ravindranath1, Hemalatha Srinivasan2
1School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science & Technology, Vandalur, Chennai, 600048, India.
Abstract:
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.
Insights
Researchers identified a novel isoquinoline alkaloid from shallots (Allium ascalonicum) that effectively targets Matrix metalloproteinases (MMPs) involved in ovarian cancer metastasis. This compound shows promise for developing new treatments for advanced ovarian cancer.
Area of Science:
- Oncology
- Pharmacology
- Computational Chemistry
Background:
- Ovarian carcinoma is a leading cause of gynecological cancer deaths due to late-stage diagnosis and metastasis.
- Matrix metalloproteinases (MMPs), specifically MMP14, MMP2, and MMP9, are key drivers of ovarian cancer cell migration and extracellular matrix degradation.
- Targeting MMPs presents a potential therapeutic strategy for inhibiting ovarian cancer progression.
Purpose of the Study:
- To identify and evaluate anti-cancer phyto-nutraceuticals from Allium ascalonicum (shallots) as potential inhibitors of MMPs involved in ovarian cancer metastasis.
- To computationally assess the binding affinity and molecular interactions of shallot compounds with target MMPs.
Main Methods:
- Molecular docking simulations were performed using predominant MMPs (MMP14, MMP2, MMP9) as target proteins and phyto-nutraceuticals from Allium ascalonicum.
- The best-docked phyto-nutraceutical was further analyzed using molecular dynamic simulations to assess interaction stability and conformational changes.
- Bioavailability scores of the identified compound were evaluated.
Main Results:
- A novel isoquinoline alkaloid from Allium ascalonicum demonstrated significant binding affinity to target MMPs, outperforming the standard drug Melphalan in docking studies.
- Molecular dynamic simulations confirmed stable interactions between the isoquinoline alkaloid and MMPs, indicating potential for inhibiting their function.
- The study identified a potent phyto-nutraceutical with favorable bioavailability for targeting MMPs in ovarian cancer.
Conclusions:
- Allium ascalonicum contains a promising novel isoquinoline alkaloid capable of interacting with MMPs to impede ovarian cancer progression and metastasis.
- This phyto-nutraceutical represents a potential lead compound for developing novel, sustainable medications for metastasized ovarian cancer.
- Further research into shallot-derived compounds could unlock new therapeutic avenues for gynecological cancers.
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
01:24Regulation of Angiogenesis and Blood Supply