Inhibition of Intracellular ROS Accumulation by Formononetin Attenuates Cisplatin-Mediated Apoptosis in LLC-PK1 Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Mar 15

PMID 29534504

Citations 17

Authors

Haesol Lee

Dahae Lee

Ki Sung Kang

Ji Hoon Song

You-Kyoung Choi

Affiliations

Soon will be listed here.

Abstract

Cisplatin is a well-known anticancer drug frequently used for treating solid tumors, including ovarian, testicular, bladder, and cervical tumors. However, usage of cisplatin has been limited because of its adverse effects, particularly nephrotoxicity. Therefore, the present study sought to investigate the protective effect of formononetin against cisplatin-induced cytotoxicity in LLC-PK1 pig kidney epithelial cells as well as the anticancer effect of cisplatin in three different human cervical cancer cell lines, including HeLa, SiHa, and CaSKi cells. We first demonstrated that formononetin strongly prevented cisplatin-induced LLC-PK1 cell death. Although formononetin had no anticancer effect, it did not interrupt the anticancer effect of cisplatin in human cervical carcinoma cell lines. Furthermore, the treatment with formononetin reduced reactive oxygen species (ROS) accumulation and chromatin condensation. The percentage of Annexin V-positive cells also increased following cisplatin treatment. Finally, formononetin-inhibited c-Jun N-terminal kinase (JNK) phosphorylation, cleavage of caspase-8 and caspase-3, and the ratio of Bax to Bcl-2 increased with cisplatin. Taken together, these findings suggest that formononetin may be a possible option to prevent nephrotoxicity induced by cisplatin during treatment for cervical cancer.

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