Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding

Abstract

Context 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

Acknowledgments

The authors acknowledge the Higher Education Commission Pakistan for funding this project under Post-Doctoral Fellowship (Ref:2-6(14)/PDFP/HEC/2013/08). This work was done as part of postdoctoral fellowship by corresponding author and was performed at Discipline of Biomedical Science, School of Medicine, The University of Sydney, Australia. The corresponding author is currently working as Assistant Professor at Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report that they have no conflicts of interest for this work.