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Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells

Department of Nursery, Tzu Hui Institute of Technology; Pingtung, Taiwan

CJ Huang

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

JS Cheng

Department of Medicine, Yongkang Veterans Hospital, Tainan, Taiwan

SI Liu

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

IS Chen

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

JY Tsai

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

CT Chou

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

PL Tseng

Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

CR Jan

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan crjan{at}isca.vghks.gov.tw

The effect of fendiline on cytosolic free Ca²⁺ concentrations ([Ca²⁺]_i) and proliferation has not been explored in human oral cancer cells. This study examined whether fendiline altered Ca²⁺ levels and caused cell death in OC2 human oral cancer cells. [Ca²⁺]_i and cell viability were measured using the fluorescent dyes fura-2 and WST-1, respectively. Fendiline at concentrations above 10 µM increased [Ca²⁺]_i in a concentration-dependent manner. The Ca²⁺ signal was reduced partly by removing extracellular Ca²⁺. The fendiline-induced Ca²⁺ influx was sensitive to blockade of L-type Ca²⁺ channel blockers. In Ca²⁺-free medium, after pretreatment with 50 µM fendiline, 1 µM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor)-induced [Ca²⁺]_i rises were inhibited; and conversely, thapsigargin pretreatment nearly abolished fendiline-induced [Ca²⁺]_i rises. Inhibition of phospholipase C with 2 µM U73122 did not change fendiline-induced [Ca²⁺]_i rises. At concentrations between 5 and 25 µM, fendiline killed cells in a concentration-dependent manner. The cytotoxic effect of 15 µM fendiline was not reversed by prechelating cytosolic Ca²⁺ with BAPTA/AM. Collectively, in OC2 cells, fendiline induced [Ca²⁺]_i rises by causing Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx from L-type Ca²⁺ channels. Furthermore, fendiline-caused cytotoxicity was not via a preceding [Ca²⁺]_i rise.

Key Words: Ca2+ fendiline • Fura-2 • oral cancer cells • thapsigargin

Human & Experimental Toxicology, Vol. 28, No. 1, 41-48 (2009)
DOI: 10.1177/0960327108097436


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