Effect of 2,5-dimethylphenol on Ca(2+) movement and viability in PC3 human prostate cancer cells.
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 Ca(2+ )signaling and cyotoxicity has never been explored in any culture cells. This study explored the effect of 2,5-dimethylphenol on cytosolic free Ca(2+ )levels ([Ca(2+)]i) and cell viability in PC3 human prostate cancer cells. 2,5-Dimethylphenol at concentrations between 500 μM and 1000 μM evoked [Ca(2+)]i rises in a concentration-dependent manner. This Ca(2+ )signal was inhibited by approximately half by the removal of extracellular Ca(2+). 2,5-Dimethylphenol-induced Ca(2+ )influx was confirmed by Mn(2+)-induced quench of fura-2 fluorescence. Pretreatment with the protein kinase C (PKC) inhibitor GF109203X, nifedipine or the store-operated Ca(2+ )entry inhibitors (econazole or SKF96365) inhibited 2,5-dimethylphenol-induced Ca(2+ )signal in Ca(2+)-containing medium by ∼30%. Treatment with the endoplasmic reticulum Ca(2+ )pump inhibitor thapsigargin in Ca(2+)-free medium abolished 2,5-dimethylphenol-induced [Ca(2+)]i rises. Conversely, treatment with 2,5-dimethylphenol abolished thapsigargin-induced [Ca(2+)]i rises. Inhibition of phospholipase C (PLC) with U73122 reduced 2,5-dimethylphenol-evoked [Ca(2+)]i rises by ∼80%. 2,5-Dimethylphenol killed cells at concentrations of 350-1000 μM in a concentration-dependent fashion. Chelation of cytosolic Ca(2+ )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 [Ca(2+)]i rises that involved Ca(2+ )entry through PKC-regulated store-operated Ca(2+ )channels and PLC-dependent Ca(2+ )release from the endoplasmic reticulum. 2,5-Dimethylphenol induced cytotoxicity in a Ca(2+)-independent manner.
a Department of Rehabilitation , Kaohsiung Veterans General Hospital Tainan Branch , Tainan , Taiwan , ROC .
Jue-Long
JL
Wang
b Department of Nursing , Division of Basic Medical Sciences, Chang Gung Institute of Technology , Chia-Yi, Taiwan , ROC .|c Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology , Chia-Yi, Taiwan , ROC .
Chiang-Ting
CT
Chou
d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan , ROC .
Wei-Zhe
WZ
Liang
e Department of Pathology and Laboratory Medicine , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan , ROC .
Jeng-Hsien
JH
Yeh
f Department of Nursing , Tzu Hui Institute of Technology , Pingtung , Taiwan , ROC .
Chun-Chi
CC
Kuo
g School of Pharmacy, China Medical University , Taichung , Taiwan , ROC .
Chao-Ying
CY
Lee
h Department of Pharmacy , Tajen University , Pingtung , Taiwan , ROC.
Pochuen
P
Shieh
h Department of Pharmacy , Tajen University , Pingtung , Taiwan , ROC.
Daih-Huang
DH
Kuo
h Department of Pharmacy , Tajen University , Pingtung , Taiwan , ROC.
Fu-An
FA
Chen
d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan , ROC .
Chung-Ren
CR
Jan
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008345:Manganese / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D014992:Xylenes / Q000494:pharmacology*
C511844:2,5-dimethylphenol; D015220:Calcium Channels; D014992:Xylenes; D008345:Manganese; D010738:Type C Phospholipases; D002118:Calcium
2,5-dimethylphenol; Ca2+; endoplasmic reticulum; phospholipase C; prostate cancer cells; store-operated Ca2+ entry