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J. F. Whitfield, A. L. Boynton, J. P. MacManus, R. H. Rixon, M. Sikorska, B. Tsang, P. R. Walker and S. H. Swierenga, “The Roles of Calcium and Cyclic AMP in Cell Proliferation,” Annals of the New York Academy of Sciences, Vol. 339, No. 1, 1980, pp. 216-240. doi:10.1111/j.1749-6632.1980.tb15980.x

has been cited by the following article:

• TITLE: Exploiting MCF-7 Cells’ Calcium Dependence with Interlaced Therapy

  AUTHORS: Jonathan Pottle, Chengrong Sun, Lloyd Gray, Ming Li

  KEYWORDS: Breast Cancer; Calcium; Calcium Channel Blockers; Ion Channels; Interlaced Therapy

  JOURNAL NAME: Journal of Cancer Therapy, Vol.4 No.7A, July 22, 2013

  ABSTRACT: The purpose of this study is to demonstrate MCF-7 cells’ dependence on calcium for growth and to exploit that dependence to improve chemotherapy efficacy. Fura-2 fluorescence imaging shows that MCF-7 cells maintain a higher basal intracellular calcium concentration than non-tumorigenic MCF-10A cells. Blocking T-type calcium channels with mibefradil reduced MCF-7 intracellular calcium concentration. Flow cytometry shows that knocking down T-type calcium channel expression with siRNA caused an increase in MCF-7 cells in G1 phase and a decrease in cells in S phase. Proliferation assays of MCF-7 cells treated with EGTA and thapsigargin reveal the dependence of MCF-7 cell growth on extracellular and intracellular calcium sources, respectively. In vitro, interlaced treatment that alternated the T-type calcium channel blocker NNC-55-0396 with paclitaxel more effectively reduced MCF-7 cell number than chemotherapy alone. In a mouse in vivo model, interlaced mibefradil and paclitaxel more effectively reduced MCF-7 xenograft size than chemotherapy alone. These findings indicate that MCF-7 cells are dependent on calcium for proliferation, particularly in passing the G1/S cell cycle checkpoint. Further, this dependence on calcium can be exploited by alternating treatment with T-type calcium channel blockers with paclitaxel in an interlaced therapy scheme that increases the efficacy of the chemotherapy.