TY - JOUR AB - Isoliquiritigenin (ISL) is a flavonoid with chalcone structure that has been noted in licorice and shallot, which are generally used in traditional Chinese medicine. ISL has demonstrated various pharmacological effects including antioxidant, anti-inflammatory and antitumor activity. However, the molecular mechanisms underlying the anticancer effects of ISL remain poorly understood. The present study revealed that ISL significantly decreased viability and induced apoptosis in human renal carcinoma Caki cells. The ISL-induced apoptosis was associated with the cleavage of caspase-9, -7 and -3, and that of PARP. Moreover, ISL increased the expression of pro-apoptotic protein Bax and diminished the expression of anti-apoptotic protein Bcl-2, and Bcl-xl, thereby increasing cytochrome c release. Treatment of cells with ISL also induced the expression of p53 through downregulation of murine double minute 2 (Mdm2). Furthermore, ISL generated reactive oxygen species (ROS), and pretreatment with ROS scavenger N-acetyl cysteine (NAC) and NADPH oxidase inhibitor diphenyleneiodonium abrogated the ISL-induced apoptosis. One of the key oncogenic signaling pathways is mediated through signal transducer and activator of transcription 3 (STAT3), which promotes abnormal cell proliferation. Incubation of cells with ISL markedly diminished phosphorylation and DNA binding activity of STAT3, and reduced expression of STAT3 responsive gene products, such as cyclin D1 and D2. ISL also attenuated constitutive phosphorylation of upstream kinase, Janus-activated kinase 2 (Jak2). Pretreatment with NAC abrogated the inhibitory effect of ISL on activation of STAT3 and blocked the cleavage of caspase-9, -7 and -3, and that of PARP in Caki cells. Taken together, the present study provides the first report that ISL induces apoptosis in Caki cells via generation of ROS, which causes induction of p53 and inhibition of the STAT3 signaling pathway. AD - College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea AU - Kim,Do-Hee AU - Park,Ji ,Eun AU - Chae,In ,Gyeong AU - Park,Geumi AU - Lee,Sooyeun AU - Chun,Kyung-Soo DA - 2017/07/01 DO - 10.3892/or.2017.5677 EP - 583 IS - 1 JO - Oncol Rep KW - isoliquiritigenin apoptosis reactive oxygen species signal transducer and activator of transcription 3 renal cancer PY - 2017 SN - 1021-335X 1791-2431 SP - 575 ST - Isoliquiritigenin inhibits the proliferation of human renal carcinoma Caki cells through the ROS-mediated regulation of the Jak2/STAT3 pathway T2 - Oncology Reports TI - Isoliquiritigenin inhibits the proliferation of human renal carcinoma Caki cells through the ROS-mediated regulation of the Jak2/STAT3 pathway UR - https://doi.org/10.3892/or.2017.5677 VL - 38 ER -