Carnosic acid induces apoptosis through inactivation of Src/STAT3 signaling pathway in human renal carcinoma Caki cells

  • Authors:
    • Ji Eun Park
    • Byoungduck Park
    • In Gyeong Chae
    • Do-Hee Kim
    • Juthika Kundu
    • Joydeb Kumar Kundu
    • Kyung-Soo Chun
  • View Affiliations

  • Published online on: February 29, 2016     https://doi.org/10.3892/or.2016.4642
  • Pages: 2723-2732
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Abstract

Carnosic acid (CA), the major bioactive compound of Rosmarinus officinalis L., has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of CA remain poorly understood. In the present study, we investigated that CA significantly reduced the viability of human renal carcinoma Caki cells. CA-induced apoptosis was connected with the cleavage of caspase-9, -7 and -3, and that of PARP. Moreover, CA increased the expression of pro-apoptotic protein Bax and diminished the expression of anti-apoptotic protein Bcl-2 and Bcl-xL, thereby releasing cytochrome c into the cytosol. Treatment with CA in Caki cells also induced the expression of p53 and its target gene product, p27, through down-regulation of Murine double minute-2 (Mdm2). Furthermore, CA generated reactive oxygen species (ROS), and pretreatment with ROS scavenger N-acetyl cysteine (NAC) abrogated CA-induced cleavage of PARP and expression of p53. One of the key oncogenic signals is mediated through signal transducer and activator of transcription-3 (STAT3), which promotes abnormal cell proliferation. Incubation of cells with CA markedly diminished the phosphorylation of STAT3 and its upstream, Src, and reduced the expression of STAT3 responsive gene products, such as D-series of cyclins and survivin. Taken together, the present study revealed that CA induced apoptosis in Caki cells by induction of p53 and suppression of STAT3 signaling.
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May-2016
Volume 35 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Park JE, Park B, Chae IG, Kim D, Kundu J, Kundu JK and Chun K: Carnosic acid induces apoptosis through inactivation of Src/STAT3 signaling pathway in human renal carcinoma Caki cells. Oncol Rep 35: 2723-2732, 2016
APA
Park, J.E., Park, B., Chae, I.G., Kim, D., Kundu, J., Kundu, J.K., & Chun, K. (2016). Carnosic acid induces apoptosis through inactivation of Src/STAT3 signaling pathway in human renal carcinoma Caki cells. Oncology Reports, 35, 2723-2732. https://doi.org/10.3892/or.2016.4642
MLA
Park, J. E., Park, B., Chae, I. G., Kim, D., Kundu, J., Kundu, J. K., Chun, K."Carnosic acid induces apoptosis through inactivation of Src/STAT3 signaling pathway in human renal carcinoma Caki cells". Oncology Reports 35.5 (2016): 2723-2732.
Chicago
Park, J. E., Park, B., Chae, I. G., Kim, D., Kundu, J., Kundu, J. K., Chun, K."Carnosic acid induces apoptosis through inactivation of Src/STAT3 signaling pathway in human renal carcinoma Caki cells". Oncology Reports 35, no. 5 (2016): 2723-2732. https://doi.org/10.3892/or.2016.4642