Abstract 5566: Carnosic acid induces apoptosis through inhibition of STAT3 signaling and production of ROS in human colon cancer HCT116 cells

Abstract

Abstract Carnosic acid (CA), the main antioxidant compound of Rosmarinus officinalis L., has been shown to display anticancer activity. However, the molecular mechanisms underlying the anticancer effects of CA remain poorly understood. This study revealed that treatment with CA significantly reduced the cell viability and induced apoptosis in HCT116 cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, -7 and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression. CA inhibited the constitutive phosphorylation, the DNA binding and the reporter gene activity of signal transducer and activator of transcription-3 (STAT3) in HCT116 cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) and Src kinases. Moreover, CA attenuated the expression of STAT3 target gene products, such as survivin, cylcin D1, D2, and D3. Since ROS is a universal entity mediating apoptosis, we examined whether CA induced apoptosis via ROS formation. Treatment with CA generated ROS and pretreatment with ROS scavenger N-acetyl cysteine (NAC) rescued cells from apoptosis by abrogating the inhibitory effect of CA on the activation of JAK2-STAT3 and Src-STAT3 signaling pathways and rescued cells from CA-induced apoptosis by blocking the induction of p53, and the cleavage of caspase-3 and PARP. In conclusion, CA induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway. Citation Format: In Gyeong Chae, Mi-Hee Yu, Ki-Woong Park, Kyung-Soo Chun. Carnosic acid induces apoptosis through inhibition of STAT3 signaling and production of ROS in human colon cancer HCT116 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2015-5566