Growth inhibitory effects of pMC540 and merodantoin on established MCF-7 human breast tumor xenografts.
The effect of preactivated merocyanine 540 (pMC540) and one of its chemically synthesized active isolate merodantoin on established human MCF-7 human breast tumor xenografts was investigated. Preactivation is a novel photochemical method for the production of chemotherapeutic compounds that exert their biological effects independent of light. These compounds thus produced, are cytotoxic to human breast cancer cells in vitro and in vivo but only minimally cytotoxic towards normal cells. Nude mice bearing established breast tumors (with or without exogenous estradiol) received injections of pMC540 (250 mg/kg) or merodantoin (75 mg/kg) with or without concurrent treatment with tamoxifen. Treatment with pMC540 and merodantoin caused a 74% and 84% inhibition of tumor growth respectively. Combination of these drugs with tamoxifen did not produce a significant enhancement of growth inhibition. In the absence of exogenous estradiol, identical treatment with pMC540 and merodantoin resulted in 41% and 25% inhibition of tumor growth respectively. Both agents caused a significant (59%) inhibition of growth of estrogen independent human breast tumors established from MDA-MB-435 cells. These results show that photochemically generated novel compounds in pMC540 are effective in suppressing the growth of established human MCF-7 and MDA-MB-435 breast tumor xenografts.
Sharma
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Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75226, USA.
Gulliya
K S
KS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight; D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000172:deficiency / Q000502:physiology; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011744:Pyrimidinones; D013629:Tamoxifen; C089291:merodantoin; D005031:Ethylenethiourea; D004958:Estradiol; C003954:merocyanine dye