Platinum anticancer agents and antidepressants: desipramine enhances platinum-based cytotoxicity in human colon cancer cells.
Platinum anticancer agents and antidepressants: desipramine enhances platinum-based cytotoxicity in human colon cancer cells.
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DOI：
10.1007/s00775-011-0836-1
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发表时间：
2012-01
影响因子：
3
通讯作者：
Farrell, Nicholas P.
中科院分区：
文献类型：
--
作者：
Kabolizadeh, Peyman;Engelmann, Brigitte J.;Pullen, Nicholas;Stewart, Jennifer K.;Ryan, John J.;Farrell, Nicholas P.
A unique synergistic effect on platinum drug cytotoxicity is noted in the presence of the tricyclic anti-depressant desipramine. Desipramine is used for treating neuropathic pain, particularly in prostate cancer patients. The clinically used drugs cisplatin (cis-[PtCl2(NH3)2]), oxaliplatin [1,2-diaminocyclohexaneoxalatoplatinum(II)], and the cationic trinuclear agent BBR3464 [{trans-PtCl(NH3)2}2-μ-(trans-Pt(NH3)2(H2N(CH2)6NH2)2)]4+, which has undergone evaluation in phase II clinical trials for activity in lung and ovarian cancers, were evaluated. Surprisingly, desipramine greatly augments the cytotoxicity of all the platinum-based chemotherapeutics in HCT116 colorectal carcinoma cell lines. Desipramine enhanced cellular accumulation of cisplatin, but had no effect on the accumulation of oxaliplatin or BBR3464, suggesting that enhanced accumulation could not be a consistent means by which desipramine altered the platinum-drug-mediated cytotoxicity. The desipramine/cisplatin combination resulted in increased levels of p53 as well as mitochondrial damage, caspase activation, and poly(ADP ribose) polymerase cleavage, suggesting that desipramine may synergize with cisplatin more than with other platinum chemotherapeutics partly by activating distinct apoptotic pathways. The study argues that desipramine may be a means of enhancing chemoresponsiveness of platinum drugs and the results warrant further investigation. The results emphasize the importance of understanding the differential pharmacological action of adjuvants employed in combinations with cancer chemotherapeutics.
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DOI：
10.1158/1078-0432.ccr-08-2081
发表时间：
2009-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jandial DD;Farshchi-Heydari S;Larson CA;Elliott GI;Wrasidlo WJ;Howell SB
通讯作者：
Howell SB
影响因子：
3.1
作者：
Arimochi, Hideki;Morita, Kyoji
通讯作者：
Morita, Kyoji
DOI：
10.1039/c0cc01254h
发表时间：
2010-09-28
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Mangrum JB;Farrell NP
通讯作者：
Farrell NP
影响因子：
7.3
作者：
Colmenarejo, G;Alvarez-Pedraglio, A;Lavandera, JL
通讯作者：
Lavandera, JL
影响因子：
5
作者：
Arimochi, Hideki;Morita, Kyoji
通讯作者：
Morita, Kyoji