title: The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells.
abstract: Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2) cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM) for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.
authors.affiliation: Department of Pathology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Ju
authors.affiliation: Department of Pathology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Jun Gue
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Institute for Medical Sciences, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Hyun Ock
authors.initials: HO
authors.lastname: Pae
authors.affiliation: Department of Neuropsychiatry, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Yeoung Su
authors.initials: YS
authors.lastname: Lyu
authors.affiliation: Department of Pathology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea ; Research Center of Traditional Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Byung Hun
authors.initials: BH
authors.lastname: Jeon