Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.

Abstract

The effect of the carcinogen safrole on intracellular Ca2+ movement and cell proliferation has not been explored previously. The present study examined whether safrole could alter Ca2+ handling and growth in human oral cancer OC2 cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at a concentration of 325 microM started to increase [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 40% by removing extracellular Ca2+, and was decreased by 39% by nifedipine but not by verapamil or diltiazem. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) barely induced a [Ca2+]i rise; in contrast, addition of safrole after thapsigargin treatment induced a small [Ca2+]i rise. Neither inhibition of phospholipase C with 2 microM U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 1 microM safrole did not alter cell proliferation, but incubation with 10-1000 microM safrole increased cell proliferation by 60+/-10%. This increase was not reversed by pre-chelating Ca2+ with 10 microM of the Ca2+ chelator BAPTA. Collectively, the data suggest that in human oral cancer cells, safrole induced a [Ca2+]i rise by causing release of stored Ca2+ from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx via nifedipine-sensitive Ca2+ entry. Furthermore, safrole can enhance cell growth in a Ca2+-independent manner.

• Authors: Jong-Khing Huang, Chun-Jen Huang, Wei-Chuan Chen, Shiuh-Inn Liu, Shu-Shong Hsu, Hong-Tai Chang, Li-Ling Tseng, Chiang-Ting Chou, Chih-Hung Chang, Chung-Ren Jan
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 372 Issue 1 Pg. 88-94 (Jul 2005) ISSN: 0028-1298 [Print] Germany
• PMID: 16080004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Carcinogens
• Thapsigargin
• Calcium-Transporting ATPases
• Nifedipine
• Safrole
• Calcium

Topics

• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Signaling (drug effects)
• Calcium-Transporting ATPases (antagonists & inhibitors)
• Carcinogens
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum (drug effects, enzymology)
• Humans
• Nifedipine (pharmacology)
• Safrole
• Thapsigargin (pharmacology)
• Time Factors