Carboplatin and epigallocatechin-3-gallate synergistically induce cytotoxic effects in esophageal cancer cells

Fatemeh Taghvaei; Sepideh Jafarzadeh Rastin; Attabak Toofani Milani; Zakieh Rostamzadeh Khameneh; Forough Hamini; Mohammad Aziz Rasouli; Keivan Asghari; Amir Mohammad Rekabi Shishavan; Meysam Ebrahimifar; Siamak Rashidi

doi:10.4103/1735-5362.314822

Carboplatin and epigallocatechin-3-gallate synergistically induce cytotoxic effects in esophageal cancer cells

Res Pharm Sci. 2021 May 12;16(3):240-249. doi: 10.4103/1735-5362.314822. eCollection 2021 Jun.

Affiliations

¹ Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Science, Yazd, I.R. Iran.
² Department of Biochemistry, Medicine Faculty, Tabriz Branch, Islamic Azad University, Tabriz, I.R. Iran.
³ Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, I.R. Iran.
⁴ Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, I.R. Iran.
⁵ Vice Chancellor for Educational and Research, Kowsar Hospital, Kurdistan University of Medical Sciences, Sanandaj, I.R. Iran.
⁶ Department of Toxicology, Faculty of Pharmacy, Shahreza Azad University, Shahreza, I.R. Iran.
⁷ Tohid Hospital, Kurdistan University of Medical Sciences, Sanandaj, I.R. Iran.

Abstract

Background and purpose: We aimed at evaluating the effects of combinatorial treatments with carboplatin and epigallocatechin-3-gallate (EGCG) on the KYSE-30 esophageal cancer (EC) cell line and elucidate the underlying mechanisms.

Experimental approach: EC cells were harvested and exposed to increasing concentrations of carboplatin and EGCG to construct a dose-response plot. Cell inhibitory effects were assessed by the MTT method and apoptosis-related gene expression levels (caspases 8 and 9) and Bcl-2 mRNA were detected using real-time polymerase chain reaction. The lactate levels in the various treated cases were analyzed using the colorimetric assay kit. In addition, total antioxidant capacity was measured.

Findings/results: The results indicated that, following treatments with carboplatin in IC₂₀, IC₂₅, and IC₁₀ concentrations when combined with EGCG in similar concentrations, synergistically decreased cell viability versus single treatments of both agents. Also, in combined treatments at IC₂₀ and IC₂₅ of both agents the gene expression ratio of caspases 8 and 9 upregulated significantly compared to monotherapies (P < 0.05). Bcl-2 gene expression ratios were decreased in double agents treated cells versus monotherapies. Following treatment of KYSE-30 cells with carboplatin and EGCG in double combinations, lactate levels were significantly decreased compared with the untreated cells and single treatments (P < 0.05). Also, in IC₂₅, IC₂₀, and IC₁₀ concentrations of both agents the total antioxidant capacity levels were decreased versus monotherapies and untreated cells.

Conclusion and implications: The presented study determined that treatment with carboplatin and EGCG was capable of promoting cytotoxicity in EC cells and inhibits the cancer progress. Combined treatments with low concentrations of carboplatin and EGCG may promote apoptosis induction and inhibit cell growth. These results confirmed the anticancer effects of carboplatin and EGCG and providing a base for additional use of EGCG to the EC treatment.

Keywords: Carboplatin; Caspase; Epigallocatechin-3-gallate; Esophageal cancer..