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In leukemic cells, the calcium release\u2010activated calcium channels provide a major pathway for calcium entry (I\n                    <jats:sub>CRAC<\/jats:sub>\n                    ) perpetuating progression through the cell cycle. Although I\n                    <jats:sub>CRAC<\/jats:sub>\n                    is under mitochondrial regulation, targeting mitochondrial function has not been exploited to control malignant cell growth. The benzothiadiazine diazoxide, which depolarized respiration\u2010dependent mitochondrial membrane potential, reduced the rate of proliferation and arrested human acute leukemic T cells in the G0\/G1 phase. Diazoxide did not alter cellular energetics, but rather inhibited the mitochondria\u2010controlled I\n                    <jats:sub>CRAC<\/jats:sub>\n                    and reduced calcium influx into tumor cells. The antiproliferative action of diazoxide was mimicked by removal of extracellular calcium or by the tyrphostin A9, an I\n                    <jats:sub>CRAC<\/jats:sub>\n                    inhibitor. Deletion of the mitochondrial genome, which encodes essential respiratory chain enzyme subunits, attenuated the inhibitory effect of diazoxide on I\n                    <jats:sub>CRAC<\/jats:sub>\n                    \u2010mediated calcium influx and cell proliferation. Thus, manipulation of mitochondrial function and associated calcium signaling provides a basis for a novel anticancer strategy.\u2014Holmuhamedov, E., Lewis, L., Bienengraeber, M., Holmuhamedova, M., Jahangir, A., Terzic, A. Suppression of human tumor cell proliferation through mitochondrial targeting.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    16, 1010\u20131016 (2002)\n                  <\/jats:p>","DOI":"10.1096\/fj.01-0996com","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T18:39:25Z","timestamp":1027881565000},"page":"1010-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Suppression of human tumor cell proliferation through mitochondrial targeting"],"prefix":"10.1096","volume":"16","author":[{"given":"EKHSON","family":"HOLMUHAMEDOV","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Diseases Departments of Medicine Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LIONEL","family":"LEWIS","sequence":"additional","affiliation":[{"name":"Section of Clinical Pharmacology Department of Medicine Dartmouth Medical School and Dartmouth Hitchkock Medical Center  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARTIN","family":"BIENENGRAEBER","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases Departments of Medicine Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MADINA","family":"HOLMUHAMEDOVA","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases Departments of Medicine Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ARSHAD","family":"JAHANGIR","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases Departments of Medicine Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANDRE","family":"TERZIC","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases Departments of Medicine Molecular Pharmacology and Experimental Therapeutics Mayo Clinic, Mayo Foundation  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.497"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/368875a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/386855a0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/31960","article-title":"Calcium oscillations increase the efficiency and specificity of gene expression","volume":"392","author":"Dolmetsch R. 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