- Cancer Pharmacology
- DNA Topoisomerase Inhibitors
- Therapy-Related Myeloid Leukemias: Chemoprevention
- Drug Resistance
Recent studies are focused on understanding the mechanisms by which the clinically effective anticancer agent etoposide (VP-16), a phenolic compound, and the environmental carcinogen, benzene, can cause therapy-related acute myelogenous leukemia (t-AML). The central testable hypothesis is that redox cycling of VP-16 and phenolic benzene metabolites initiated by myeloperoxidase (MPO) in bone marrow precursors amplifies the genotoxicity and carcinogenicity of these compounds via enhanced inhibition/poisoning of DNA topoisomerase II. Nutritional antioxidants such as vitamin C and vitamin E homologs are under investigation as a mechanism-based chemoprevention strategy to eliminate VP-16- and benzene-induced AML by reducing production of MPO-dependent free radical and electrophilic metabolites. The long-term goal of these studies is to increase the clinical efficacy of VP-16 in the treatment of cancer, and to prevent benzene leukemogenesis.
- Postdoctoral Fellow, 1980-1983, Medical College of Virginia
- PhD, 1980, Biochemical Pharmacology, SUNY at Buffalo
- Bachelor of Arts, 1974, Chemistry/Biology, Lehigh University
Kanagasabai, R., Serdar, L, Karmahapatra, S, Kientz, C.A., Ellis, J., Ritke, M.K., Elton, T.S., and Yalowich, J.C. Alternative RNA Processing of Topoisomerase IIα in Etoposide-Resistant Human Leukemia K562 Cells: Intron Retention Results in a Novel C-Terminal Truncated 90-kDa Isoform. J. Pharm. Expt. Ther.; 2017 Jan: 360(1): 152-163.
Hasinoff, B.B., Wu, X, Patel, D., Kanagabasai, R., Karmahapatra, S., and Yalowich, J.C. Mechanisms of action and reduced cardiotoxicity of pixantrone; a topoisomerase II targeting agent with specificity for the topoisomerase IIα isoform. J. Pharm Expt. Ther.; 2016 Feb;356(2):397-409.
Nagre, N.N., Wang, S., Kellet, T., Kanagasabai, R., Deng, J., Nishi, M., Shilo, K., Oeckler, R.A., Yalowich, J.C., Takashima, H., Christman, J.W., Hubmayr, R.D., and Zhao, X. TRIM72 modulates caveolar endocytosis in repair of lung cells. Am. J. Physiol. Lung Cell Mol. Physiol.; 2016 Mar 1;310(5):L452-64.
Elton, T.S. and Yalowich J.C. Experimental procedures to identify and validate specific mRNA targets of miRNAs. (http://dx.doi.org/10.17179/excli2015-319) EXCLI J. 2015 Jul 2;14:758-90.
Hasinoff, B.B., Wu, X., Yadav, A.A., Patel, D., Zhang, H., Wang, D.S., Chen, Z.S., and Yalowich, J.C. Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II). Biochem. Pharmacol. , 2015 Feb 1; 93(1): 266-76.
Yadav, A.A., Wu, X., Patel, D., Yalowich, J.C., and Hasinoff, B.B.. Structure-based design, synthesis and biological testing of etoposide analog epipodophyllotoxin-N-mustard hybrid compounds designed to covalently bind to topoisomerase II and DNA. Biorg. Med. Chem., 2014 : DOI Nov 1; 22(21): 5935-49.
Ren, Y., Lantvit, D.D., Deng, Y., Kanagasabai, R., Gallucci, J.C., Ninh, T.N., Chai H.B., Soejarto, D.D., Fuchs J.R., Yalowich, J.C., Yu, J., Swanson, S.M., and Kinghorn, A.D. Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei. J. Nat. Prod. 2014 Jun 27; 77(6): 1494-504.
Hasinoff, B.B., Wu, X., Nitiss, J.L., Kanagasabai, R., and Yalowich, J.C. The anticancer multi-kinase inhibitor dovitinib also targets topoisomerase I and topoisomerase II. Biochem. Pharmacol. 2012 Dec 15; 84 (12): 1617-26.
Yalowich, J.C.; Wu, X.; Zhang, R.; Kanagasabai, R.; Hornbaker, M.; Hasinoff, B.B. The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIα.Biochemical pharmacology. 2012 Jul 1;84(1):52-8
Zhang, R., Wu, X., Yalowich, J.C., and Hasinoff, B.B. Design, synthesis, and biological evaluation of a novel series of bisintercalating DNA-binding piperazine-linded bisanthrapyrazole compounds as anticancer agents. Bioorganic & medicinal chemistry. 2011; Dec 1;19(23): 7023-7032
Wu, X, Yalowich, J.C., and Hasinoff, B.B. Cadmium is a catalytic inhibitor of DNA topoisomerase II. Journal of inorganic biochemistry.. 2011; 105(6): 833-838
- Am J Physiol Lung Cell Mol Physiol. 2016 Mar 1;310(5):L452-64
- J Pharmacol Exp Ther. 2016 Feb;356(2):397-409
- Biochem Pharmacol. 2015 Feb 1;93(3):266-76
- EXCLI J. 2015;14:758-90
- Bioorg Med Chem. 2014 Nov 1;22(21):5935-49
- J. Nat. Prod. 2014 Jun 27; 77(6): 1494-504
- Biochem Pharmacol. 2012 Jul 1;84(1):52-8