Cycloartenyl Ferulate Inhibits Paraquat-Induced Apoptosis in HK-2 Cells With the Involvement of ABCC1

• Published in: Journal of cellular biochemistry Vol. 117; no. 4; pp. 872 - 880
• Main Authors: Hong, Guang-Liang, Liu, Jia-Ming, Zhao, Guang-Ju, Tan, Jia-Ping, Wu, Bin, Li, Meng-Fang, Liang, Guang, Qiu, Qiao-Meng, Lu, Zhong-Qiu
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc
• Subjects: ABCC1; ABCC1 protein; Accumulation; APOPTOSIS; Apoptosis - drug effects; ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters - deficiency; ATP-Binding Cassette Transporters - genetics; Biocompatibility; Cell Line; Cell survival; Coumaric Acids - pharmacology; CYCLOARTENYL FERULATE; Cytotoxicity; Cytotoxins - antagonists & inhibitors; Cytotoxins - toxicity; DNA fragmentation; DNA Fragmentation - drug effects; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Flow cytometry; G1 Phase Cell Cycle Checkpoints - drug effects; Gene Expression Regulation; High-performance liquid chromatography; Humans; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Liquid chromatography; Molecular modelling; Neoplasm Proteins - deficiency; Neoplasm Proteins - genetics; NEPHROTOXICITY; PARAQUAT; Paraquat - antagonists & inhibitors; Paraquat - toxicity; Protective Agents - pharmacology; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; siRNA; Toxicity; APOPTOSIS; ABCC1; CYCLOARTENYL FERULATE; PARAQUAT; NEPHROTOXICITY
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25370

ABSTRACT Nephrotoxicity induced by chemicals such as paraquat (PQ) is a common clinical phenomenon; therefore, searching for drugs with renal protective effect is of a great practical significance. Our previous investigation found that cycloartenyl ferulate (CF) can antagonize the cytotoxic effect of PQ, and recent studies also revealed a variety of bioactivities of CF. However, specific molecular mechanisms underlying the protective effect of CF have not been explored yet. HPLC detection of PQ content indicated that CF reduced PQ accumulation in HK‐2 cells and thereby improved cell survival. Western blot results showed that both PQ and CF did not affect the expression of ABCB1; however, while PQ suppressed the expression of ABCC1, CF upregulated ABCC1 expression and thereby reversed the inhibitory effect of PQ on ABCC1 expression. Meanwhile, HK‐2 cells did not express ABCG2. When the expression of ABCC1 was knocked down with siRNA, the inhibitory effect of CF on intracellular PQ accumulation was blocked. Further flow cytometric analysis showed that while PQ significantly induced the appearance of sub‐G1 apoptotic peak in cells, CF evidently inhibited apoptosis. TUNEL‐DAPI double‐staining also detected that PQ significantly induced the occurrence of DNA fragmentation in cells, whereas CF effectively inhibited the effect of PQ. Further results showed that ABCC1 siRNA effectively abolished the protective effect of CF on PQ‐induced apoptosis. Taken together, these data demonstrated that in HK‐2 cells, CF could antagonize PQ‐induced toxicity with the involvement of regulatiion of ABCC1 protein expression, which provides a new strategy for treatments of nephrotoxicity. J. Cell. Biochem. 117: 872–880, 2016. © 2015 Wiley Periodicals, Inc.