PURPOSE: Cervical cancer causes considerable mortality in women world over and the current treatment options create severe adverse effects. Hence, there is an urgent need to develop novel and efficient treatment regimens for cervical cancer. Herein, we examined the anticancer effects of a natural coumarin, Scopoletin, against a panel of cervical cancer cell lines. METHODS: The antiproliferative effect of Scopoletin was examined by cell counting and colony formation assays. Apoptosis was detected by acridine orange (AO) ethidium promide (EB) staining. Cell cycle distribution was determined by flow cytometry. Cell invasion was examined by Boyden chamber assay. Protein expression was checked by western blotting. RESULTS: Scopoletin inhibited the growth of all the cell lines and the IC50 ranged between 7.5 to 25 µM. Nonetheless, the cytotoxic effects of Scopoletin were comparatively negligible against the normal cells with an IC50 of 90 µM. Investigation of the mechanism of action, revealed that the anticancer effects of Scopoletin against the HeLa cervical cancer cells were due to induction of apoptotic cell death as indicated AO/EB staining. Scopoletin treatment also resulted in enhancement of the Bax, Caspase 3, 8 and 9 expression and decline of the Bcl-2 expression. Scopoletin also blocked the HeLa cells at G2/M checkpoint of the cell cycle. Furthermore, cell invasion assay revealed that Scopoletin inhibited the migration of the HeLa cells concentration-dependently. PI3K/AKT is an imperative pathway involved in theproliferation and tumorigenesis of cancer cells and herein it was found that Scopoletin could inhibit this pathway. CONCLUSION: Taken together, Scopoletin may prove essential in the development of novel treatment regimes for cervical cancer.
PURPOSE:Cervical cancer causes considerable mortality in women world over and the current treatment options create severe adverse effects. Hence, there is an urgent need to develop novel and efficient treatment regimens for cervical cancer. Herein, we examined the anticancer effects of a natural coumarin, Scopoletin, against a panel of cervical cancer cell lines. METHODS: The antiproliferative effect of Scopoletin was examined by cell counting and colony formation assays. Apoptosis was detected by acridine orange (AO)ethidium promide (EB) staining. Cell cycle distribution was determined by flow cytometry. Cell invasion was examined by Boyden chamber assay. Protein expression was checked by western blotting. RESULTS:Scopoletin inhibited the growth of all the cell lines and the IC50 ranged between 7.5 to 25 µM. Nonetheless, the cytotoxic effects of Scopoletin were comparatively negligible against the normal cells with an IC50 of 90 µM. Investigation of the mechanism of action, revealed that the anticancer effects of Scopoletin against the HeLa cervical cancer cells were due to induction of apoptotic cell death as indicated AO/EB staining. Scopoletin treatment also resulted in enhancement of the Bax, Caspase 3, 8 and 9 expression and decline of the Bcl-2 expression. Scopoletin also blocked the HeLa cells at G2/M checkpoint of the cell cycle. Furthermore, cell invasion assay revealed that Scopoletin inhibited the migration of the HeLa cells concentration-dependently. PI3K/AKT is an imperative pathway involved in theproliferation and tumorigenesis of cancer cells and herein it was found that Scopoletin could inhibit this pathway. CONCLUSION: Taken together, Scopoletin may prove essential in the development of novel treatment regimes for cervical cancer.