Reference

Identification of anthracycline analogs with enhanced cytotoxicity and lack of cross-resistance to adriamycin using a series of mammalian cell lines in vitro

Identification of anthracycline analogs with enhanced cytotoxicity and lack of cross-resistance to adriamycin using a series of mammalian cell lines in vitro. Hill, Bridget T.; Dennis, Lorraine Y.; Li, Xue Teng; Whelan, Richard D. H. (Lab. Cell. Chemother., Imp. Cancer Res. Fund, London WC2A 3PX, UK). Cancer Chemother. Pharmacol., 14(3), 194-201 (English) 1985. CODEN: CCPHDZ. ISSN: 0344-5704. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Using NIL 8 Syrian hamster ovary cells and 2 continuous human tumor cell lines derived from colon carcinomas, 11 anthracycline analogs were screened for in vitro cytotoxic effects by colony-forming assays. Five agents proved significantly more cytotoxic than adriamycin (ADR) [23214-92-8]: dihydroxyanthraquinone (DHAQ) [65271-80-9], mitoxantrone (DHAD) [65271-80-9], 4-demethoxydaunorubicin (4-DNR) [58957-92-9], 4'-O-tetrahydropyranyladriamycin (THP-ADR) [72496-41-4], and 4'-deoxyadriamycin (4-ADR) [63521-85-7]. In vitro, a subline of the L5178Y murine lymphoma resistant to ADR was established. This model was used to identify derivs. with potential value for overcoming ADR resistance. Three patterns of responses were obsd.: (i) complete cross-resistance with 4'-epiadriamycin [56420-45-2] and daunorubicin [20830-81-3], (ii) slight cross-resistance with 4-DNR, THP-ADR, 7-con-O-methyl-nogarol [71628-96-1] and aclacinomycin A [57576-44-0], and (iii) complete absence of cross-resistance with 4-ADR, 4'-O-methyladriamycin [77121-90-5], DHAQ, DHAD, and methylhydroxyellipticinium. These straightforward preclin. screens thus identify 3 drugs which may merit clin. evaluation, since they not only show an increased level of cytotoxicity in vitro to ADR at equiv. concns. but also overcome resistance to ADR in this murine model system.

Anti-tumor effects of Adriamycin, 4'-Epi-Adriamycin, THP-Adriamycin and Mitoxantrone on rat mammary cancer induced by 7,12-dimethyl benz (A) anthracene

Anti-tumor effects of Adriamycin, 4'-Epi-Adriamycin, THP-Adriamycin and Mitoxantrone on rat mammary cancer induced by 7,12-dimethyl benz (A) anthracene. Tominaga, Takeshi; Kitamura, Masatsugu; Yoshida, Yoko; Kosaki, Goro (Dep. Surg., Tokyo Metrop. Komagome Hosp., Japan). Gan to Kagaku Ryoho, 11(8), 1663-8 (Japanese) 1984. CODEN: GTKRDX. ISSN: 0385-0684. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Comparative studies of the antitumor effects of Adriamycin, [23214-92-8] 4'-Epi-Adrimycin [56420-45-2], 4'-o-tetrahydropyranyl-Adriamycin [72496-41-4] and Mitoxantrone [65271-80-9] on rat mammary cancer induced by 7,12-DMBA were performed. All 4 drugs were effective on the tumors. Three administrations of Adriamycin, 4'-Epi-Adriamcyin or Mitoxantrone at 1-wk intervals showed remarkable tumor regression in each group. Mitoxantrone was not so effective in comparison with the other 3 drugs. Decrease in the body wt. of the rats was most remarkably obsd. in the Mitoxantrone-treated group.