In vitro and in vivo growth suppression of MCF-7 human breast cancer by novel photoproducts and tamoxifen.
BACKGROUND
Preactivation is a novel photochemical method for the production of chemotherapeutic compounds that exert their biologic effects independent of light. The compounds that are produced, preactivated merocyanine 540 (pMC540) and merodantoin, are cytotoxic to cultured human breast cancer cells but are only minimally cytotoxic toward normal cells. Their effects against breast cancer have not been studied in vivo.


METHODS
Estrogen-stimulated human MCF-7 breast adenocarcinoma cells were grown as solid tumors in athymic carrier mice. Animals bearing defined sizes of subcutaneously transplanted solid breast tumors received injections of pMC540 (250 mg/kg) with or without concurrent treatment with tamoxifen. Growth inhibitory effects of merodantoin (N,N'-dibutyl-2-thio-4,5-imidazolidion) on the breast tumor growth were determined.


RESULTS
Direct injection of established tumors with eight doses of pMC540 (250 mg/kg) administered on alternate days resulted in significant tumor regression (P = 0.002). In three of seven animals, palpable tumors could not be detected after this treatment (16 days). Treatment through intramuscular injections (20 doses) with pMC540 (250 mg/kg) also caused a significant suppression of tumor area (P = 0.004; P = 0.0882; P = 0.0903) and a marginally significant suppression of tumor weight and volume, respectively. Combined treatment with tamoxifen and pMC540 (100 mg/kg) caused a 67% suppression of breast tumor growth. Treatment with 20 doses of merodantoin (75 mg/kg) suppressed the growth of breast tumors by 98%.


CONCLUSIONS
To the authors' knowledge, these results show for the first time that photochemically generated novel compounds in pMC540 alone and in combination with tamoxifen are effective in suppressing in vivo growth of xenografted human MCF-7 breast tumors.
Gulliya
K S
KS
Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75226.
Sharma
R K
RK
Matthews
J L
JL
Benniston
A C
AC
Harriman
A
A
Nemunaitis
J J
JJ
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D011744:Pyrimidinones / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D011744:Pyrimidinones; D013629:Tamoxifen; C089291:merodantoin; D005031:Ethylenethiourea; C003954:merocyanine dye