title: Enhancement of Cisplatin sensitivity in human cervical cancer: epigallocatechin-3-gallate.
abstract: Cisplatin is one of the effective chemotherapeutics in the treatment of several types of cancers. However, in addition to the efforts against to its toxicity, the amelioration of cisplatin sensitivity is an important point in treatment of cervical cancer. To do so, additional substances such as epigallocatechin gallate (EGCG), a polyphenol in green tea, have been used in combination with chemotherapeutics. We aimed to investigate the possible molecular pathways to potentiate cervical cancer cell (HeLa) growth inhibition by combination therapy of cisplatin and EGCG. HeLa cells were treated with EGCG (25 μM), cisplatin (250 nM), and their combination for 24 h. Cell viability was determined by MTS Assay. We analyzed the expressions of NF-κB p65, COX-2, Nrf2, HO-1, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt by Western blot analysis. Herein, we have demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of cervical cancer cells. EGCG improved efficacy of cisplatin treatment in HeLa cells by regulating NFκB p65, COX-2, p-Akt, and p-mTOR pathways, whereas it increased the expression levels of Nrf2/HO-1 in combined therapy. Our observations revealed that EGCG increases the sensitization of cisplatin to cervical cancer cells by inhibiting cell survival and inducing apoptosis.
authors.affiliation: Department of Medical Biology and Regenerative and Restorative Medicine Research Center (REMER), Faculty of Medicine, Istanbul Medipol University , Istanbul , Turkey.
authors.forename: Ulkan
authors.initials: U
authors.lastname: Kilic
authors.affiliation: Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University , Elazıg , Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
authors.affiliation: Department of Biology, Faculty of Science, Firat University , Elazıg , Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.affiliation: Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University , Istanbul , Turkey.
authors.forename: Nazli
authors.initials: N
authors.lastname: Basak
authors.affiliation: Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University , Elazıg , Turkey.
authors.forename: Cemal
authors.initials: C
authors.lastname: Orhan
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University , Istanbul , Turkey.
authors.forename: Birsen
authors.initials: B
authors.lastname: Elibol-Can
authors.affiliation: Department of Physiology, Faculty of Medicine, Istanbul Medipol University , Istanbul , Turkey.
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University , Istanbul , Turkey.
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Sahin
authors.affiliation: Winship Cancer Institute, Emory University , Atlanta, GA , USA.
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
keywords: HeLa cells; cisplatin; epigallocatechin gallate; human cervical cancer; sensitization