Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells

  • Authors:
    • Ki-Woong Park
    • Juthika Kundu
    • In-Gyeong Chae
    • Do-Hee Kim
    • Mi-Hee Yu
    • Joydeb Kumar Kundu
    • Kyung-Soo Chun
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  • Published online on: January 27, 2014     https://doi.org/10.3892/ijo.2014.2281
  • Pages: 1309-1315
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Abstract

Carnosol, an active constituent of rosemary, has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of carnosol remain poorly understood. In the present study, we found that carnosol significantly reduced the viability of human colon cancer (HCT116) cells in a concentration- and time-dependent manner. Treatment of cells with carnosol induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of poly-(ADP-ribose) polymerase (PARP). Incubation with carnosol elevated the expression of Bax and inhibited the levels of Bcl-2 and Bcl-xl. Carnosol induced expression of p53 and inhibited that of murine-double minute-2 (Mdm2). Moreover, carnosol generated reactive oxygen species (ROS), and pretreatment with N-acetyl cysteine abrogated carnosol-induced cleavage of caspase-3 and PARP. The constitutive phosphorylation, the DNA binding and reporter gene activity of signal transducer and activator of transcription-3 (STAT3) was diminished by treatment with carnosol. To further elucidate the molecular mechanisms of STAT3 inactivation, we found that carnosol attenuated the phosphorylation of Janus-activated kinase-2 (Jak2) and Src kinase. Pharmacological inhibition of Jak2 and Src inhibited STAT3 phosphorylation. Furthermore, carnosol attenuated the expression of STAT3 target gene products, such as survivin, cyclin-D1, -D2, and -D3. Taken together, our study provides the first report that carnosol induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway.
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2014-April
Volume 44 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Park K, Kundu J, Chae I, Kim D, Yu M, Kundu JK and Chun K: Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int J Oncol 44: 1309-1315, 2014.
APA
Park, K., Kundu, J., Chae, I., Kim, D., Yu, M., Kundu, J.K., & Chun, K. (2014). Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. International Journal of Oncology, 44, 1309-1315. https://doi.org/10.3892/ijo.2014.2281
MLA
Park, K., Kundu, J., Chae, I., Kim, D., Yu, M., Kundu, J. K., Chun, K."Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells". International Journal of Oncology 44.4 (2014): 1309-1315.
Chicago
Park, K., Kundu, J., Chae, I., Kim, D., Yu, M., Kundu, J. K., Chun, K."Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells". International Journal of Oncology 44, no. 4 (2014): 1309-1315. https://doi.org/10.3892/ijo.2014.2281