4.6 Article

Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion

Journal

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 701, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2021.108795

Keywords

Quercetin; Survival; Proliferation; Adhesion; Metastasis; PA-1

Funding

  1. Rajiv Gandhi National Fellowship for Students with Disabilities, UGC, New Delhi, India [F./2013-14/RGNF-2013-14D-OBC-TAM-56329]

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Research has shown that quercetin inhibits the survival and proliferation of human metastatic ovarian cancer cells by inactivating PI3K/Akt, Ras/Raf pathways, and EGFR expression. It also alters N-cadherin expression, decreases gelatinase secretion and MMP-2/-9 gene expression, and inhibits migration and adhesion of the cancer cells. These findings suggest that quercetin could be a valuable therapeutic drug for the treatment and prevention of metastatic ovarian cancer.
Ovarian cancer is the most deadly gynaecology related cancer due to its high metastasizing ability. Quercetin is the most abundant flavonoids received increased interest due to its anti-cancer properties. Although the anticancer property of quercetin is very well known, its anti-metastatic effect on metastatic ovarian cancer cells and their underlying molecular mechanism remains to be elucidated. Quercetin treatment at 50 ?M and 75 ?M concentration inhibit human metastatic ovarian cancer PA-1 cell survival and proliferation via inactivating PI3k/ Akt, Ras/Raf pathways and EGFR expression. It also alters the expression of N-cadherin in PA-1 cells. Quercetin also decreases the secretion of gelatinase enzyme, proteolytic activity of MMP-2/-9, and both MMPs gene expression in metastatic ovarian cancer PA-1 cells. In addition to this quercetin inhibits the migration of PA-1 cells. Treatment of quercetin with PA-1 cells also downregulates the tight junctional molecules such as Claudin-4 and Claudin-11 while upregulates the expression of occludin. It is further validated by cell adhesion assay in which quercetin reduces the adhesion of PA-1 ovarian cancer cells. Results suggest that quercetin inhibits cell survival, proliferation, migration, and adhesion which plays crucial role in ovarian cancer metastasis. Hence, it could be a valuable therapeutic drug for the treatment and prevention of metastatic ovarian cancer.

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