Effect of 2,5-dimethylphenol on Ca2+ movement and viability in PC3 human prostate cancer cells |
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Authors: | Jue-Long Wang Chiang-Ting Chou Wei-Zhe Liang Jeng-Hsien Yeh Chun-Chi Kuo Chao-Ying Lee |
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Affiliation: | 1. Department of Rehabilitation, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan, ROC,;2. Department of Nursing, Division of Basic Medical Sciences, Chang Gung Institute of Technology, Chia-Yi, Taiwan, ROC,;3. Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology, Chia-Yi, Taiwan, ROC,;4. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC,;5. Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC,;6. Department of Nursing, Tzu Hui Institute of Technology, Pingtung, Taiwan, ROC,;7. School of Pharmacy, China Medical University, Taichung, Taiwan, ROC, |
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Abstract: | The phenolic compound 2,5-dimethylphenol is a natural product. 2,5-Dimethylphenol has been shown to affect rat hepatic and pulmonary microsomal metabolism. However, the effect of 2,5-dimethylphenol on Ca2+?signaling and cyotoxicity has never been explored in any culture cells. This study explored the effect of 2,5-dimethylphenol on cytosolic free Ca2+?levels ([Ca2+]i) and cell viability in PC3 human prostate cancer cells. 2,5-Dimethylphenol at concentrations between 500?μM and 1000?μM evoked [Ca2+]i rises in a concentration-dependent manner. This Ca2+?signal was inhibited by approximately half by the removal of extracellular Ca2+. 2,5-Dimethylphenol-induced Ca2+?influx was confirmed by Mn2+-induced quench of fura-2 fluorescence. Pretreatment with the protein kinase C (PKC) inhibitor GF109203X, nifedipine or the store-operated Ca2+?entry inhibitors (econazole or SKF96365) inhibited 2,5-dimethylphenol-induced Ca2+?signal in Ca2+-containing medium by ~30%. Treatment with the endoplasmic reticulum Ca2+?pump inhibitor thapsigargin in Ca2+-free medium abolished 2,5-dimethylphenol-induced [Ca2+]i rises. Conversely, treatment with 2,5-dimethylphenol abolished thapsigargin-induced [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 reduced 2,5-dimethylphenol-evoked [Ca2+]i rises by ~80%. 2,5-Dimethylphenol killed cells at concentrations of 350–1000?μM in a concentration-dependent fashion. Chelation of cytosolic Ca2+?with 1,2-bis(2-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid/AM (BAPTA/AM) did not prevent 2,5-dimethylphenol’s cytotoxicity. Together, in PC3 cells, 2,5-dimethylphenol induced [Ca2+]i rises that involved Ca2+?entry through PKC-regulated store-operated Ca2+?channels and PLC-dependent Ca2+?release from the endoplasmic reticulum. 2,5-Dimethylphenol induced cytotoxicity in a Ca2+-independent manner. |
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Keywords: | Ca2+ 2,5-dimethylphenol endoplasmic reticulum phospholipase C prostate cancer cells store-operated Ca2+ entry |
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