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Growth Inhibitory Effect of Wedelolactone in Combination with Cisplatin on PA-1 Ovarian Cancer Cell Line


Affiliations
1 Department of Biochemistry, V.V. Vanniaperumal College for Women, Virudhunagar - 626001, Tamil Nadu, India
2 VRR Institute of Biomedical Sciences (Affiliated to University of Madras), Chennai - 600017, Tamil Nadu, India
 

Drug resistance and poor therapeutic outcomes are the emerging problems pertaining to cisplatin treatment in ovarian cancer. The effectiveness of the conventional chemotherapeutic medication could be improved by combining with natural drugs. In the current study, Wedelolactone (WDL) a natural coumestan, in combination with Cisplatin (Cis) was determined to be a potent anti-cancer drug as evidenced by their capacity to bring about cytotoxicity by decreasing NF-κB expression in PA-1 ovarian cancer cells. “Cell viability assays” were carried out and the effective combination of wedelolactone with Cisplatin were confirmed by PCR and western blot analysis. The determined IC50 (10µM) of WDL displayed advantageous anti-cancer effect in PA-1 cells compared to Cis treatment. Furthermore, the combination of wedelolactone (5µM) and cisplatin(3µM) also down regulated NF-κB expression which is a key player of various cancer promoting events such as drug resistance, apoptotic inhibition, inflammation and angiogenesis. WDL potentiates the sensitivity of PA-1 cells towards cisplatin by decreasing the ETS1 and P-gp expression which are involved in MDR mechanism. Overall, this study suggest that Wedelolactone can be used to sensitize ovarian tumors to standard cancer chemotherapeutics.

Keywords

Cisplatin, Drug Resistance, ETS, NF-κB, P-gp, Wedelolactone.
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  • Growth Inhibitory Effect of Wedelolactone in Combination with Cisplatin on PA-1 Ovarian Cancer Cell Line

Abstract Views: 163  |  PDF Views: 78

Authors

Gloria Jemmi Christobel Robinson
Department of Biochemistry, V.V. Vanniaperumal College for Women, Virudhunagar - 626001, Tamil Nadu, India
Shyam Sundar Jaganathan
VRR Institute of Biomedical Sciences (Affiliated to University of Madras), Chennai - 600017, Tamil Nadu, India
Abirami M. Padmanaban
VRR Institute of Biomedical Sciences (Affiliated to University of Madras), Chennai - 600017, Tamil Nadu, India
Shila Samuel
VRR Institute of Biomedical Sciences (Affiliated to University of Madras), Chennai - 600017, Tamil Nadu, India

Abstract


Drug resistance and poor therapeutic outcomes are the emerging problems pertaining to cisplatin treatment in ovarian cancer. The effectiveness of the conventional chemotherapeutic medication could be improved by combining with natural drugs. In the current study, Wedelolactone (WDL) a natural coumestan, in combination with Cisplatin (Cis) was determined to be a potent anti-cancer drug as evidenced by their capacity to bring about cytotoxicity by decreasing NF-κB expression in PA-1 ovarian cancer cells. “Cell viability assays” were carried out and the effective combination of wedelolactone with Cisplatin were confirmed by PCR and western blot analysis. The determined IC50 (10µM) of WDL displayed advantageous anti-cancer effect in PA-1 cells compared to Cis treatment. Furthermore, the combination of wedelolactone (5µM) and cisplatin(3µM) also down regulated NF-κB expression which is a key player of various cancer promoting events such as drug resistance, apoptotic inhibition, inflammation and angiogenesis. WDL potentiates the sensitivity of PA-1 cells towards cisplatin by decreasing the ETS1 and P-gp expression which are involved in MDR mechanism. Overall, this study suggest that Wedelolactone can be used to sensitize ovarian tumors to standard cancer chemotherapeutics.

Keywords


Cisplatin, Drug Resistance, ETS, NF-κB, P-gp, Wedelolactone.

References





DOI: https://doi.org/10.18311/jnr%2F2023%2F32092