Stress hormone norepinephrine (NE) has been associated with acquisition of cancer progression, and naturally occurring phytoalexin resveratrol (REV) has been known to suppress cancer growth and progression. In the present study, we determine the effect of REV on NE-induced ovarian cancer invasiveness. Pretreatment of REV significantly inhibited NE-induced ovarian cancer cell epithelial-to-mesenchymal transition with concomitant recovery of E-cadherin expression. In addition, our data showed that REV downregulates NE-induced human telomerase reverse transcriptase (hTERT) expression through inhibiting Src phosphorylation and HIF-1α expression. Further, REV reduced NE-induced Slug expression and subsequent ovarian cancer invasion. More importantly, combined treatment of REV with a pharmacological inhibitor of beta adrenergic receptor significantly attenuated NE-induced ovarian cancer invasion compared to single treatment. Therefore, we demonstrate interference of a Src and HIF-1α/hTERT/Slug signaling cascade by REV, providing potential therapeutic targets and inhibition of ovarian cancer.
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This study was supported by a Grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A2A1A01004363, NRF-2013R1A1A2A10059565, NRF-2014R1A2A1A11051091).
Conflict of Interest
The authors disclose no potential conflicts of interest.
Seung Hwa Kim and Kyung Hwa Cho have contributed equally to this work.
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Kim, S.H., Cho, K.H., Kim, Y.N. et al. Resveratrol attenuates norepinephrine-induced ovarian cancer invasiveness through downregulating hTERT expression. Arch. Pharm. Res. 39, 240–248 (2016). https://doi.org/10.1007/s12272-015-0666-8