Drug Design, Development and Therapy (Sep 2020)
Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding
Abstract
Sadia Sarwar,1,2 Jun Qing Yu,1 Humaira Nadeem,3 Fazlul Huq1 1Discipline of Biomedical Sciences, Sydney Medical School, The University of Sydney, Cumberland Campus, Sydney, NSW, Australia; 2Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 3Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, PakistanCorrespondence: Sadia Sarwar Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical SciencesRiphah International University, Islamabad, PakistanTel +92-333-5565889Email [email protected] and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells.Methods: In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action.Results: BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0).Discussion and Conclusion: This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.Keywords: HeLa, wedelolactone; WDL, betulinic acid; BA, MTT reduction assay, combination index; CI, synergism
