Inhibition of ANO1 by Cis- and Trans-Resveratrol and Their Anticancer Activity in Human Prostate Cancer PC-3 Cells

Abstract

Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 μM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 μM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer

“…In a recent study, RSV in both its cis and trans forms was shown to inhibit the activity of the Anoctamin1 (ANO1) channel (a calcium-activated chloride channel, which is involved in the proliferation, migration, and invasion of various types of cancer, including head and neck squamous cell carcinoma, lung cancer, and prostate cancer) (Carter et al, 2014). In addition, they showed how RSV also decreased the expression of ANO1 protein and mRNA in PC-3 prostate cancer cells (Jeon et al, 2023).…”

Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent

“…The trans-isomer is more stable and predominant, with more therapeutic properties [ 63 ]. Cytotoxicity studies on pancreatic cancer, breast cancer, small-cell lung carcinoma, colon cancer, and prostate cancer cell lines revealed that trans-resveratrol possesses slightly more potent cytotoxic properties than the cis-isomer, attributed to its better bioavailability and biodistribution [ 64 , 65 , 66 ]. Upon exposure to sunlight or UV radiation at 254 nm or 366 nm, trans-RSV converts into cis-RSV and vice versa.…”

Sustainable In Silico-Supported Ultrasonic-Assisted Extraction of Oligomeric Stilbenoids from Grapevine Roots Using Natural Deep Eutectic Solvents (NADES) and Stability Study of Potential Ready-to-Use Extracts

“…Stilbenoids are important phytoalexins that protect plants from pathogens [1]. Moreover, stilbenoids exhibit a number of health-promoting benefits, namely antioxidant, antiinflammatory, anticancerogenic, antiatherogenic, antiviral, and neuroprotective activities [2][3][4][5][6][7][8]. Stilbenoids are found in only a few plant families, including Vitaceae, Fabaceae, Polygonaceae, and Gnetaceae [9][10][11].…”