Krystyna Frenkel

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Krystyna Frenkel

Research Professor, Department of Environmental Medicine
Environmental Medicine

Contact Info

Address
455 First Avenue
New York, NY 10016

212/263-6610
Krystyna.Frenkel@nyumc.org


Education

1959-1964 — Warsaw University School of Chemistry, Poland, Graduate Education
1971-1974 — New York University GSAS, Graduate Education
1974-1976 — Columbia University Institute of Cancer Research, New York, NY, PostDoctoral Training

Research Summary



We showed that tumor promoters induce oxidants and DNA base oxidation in cultured and epidermal cells isolated from mice treated in vivo. Anti-tumor promoters inhibited the tumor promoter mediated inflammation, edema, neutrophil infiltration, and formation of H2O2 and of oxidized DNA bases [5-hydroxy-methyl-2'-deoxyuridine (HMdU) and 8-hydroxy-2'-deoxyguanosine (8-OHdG)]. These anti-promoters included (-) epi-gallocatechin gallate (EGCG, from green tea), caffeic acid phenethyl ester (CAPE, the propolis of honeybee hives), sarcophytol A (soft coral), and Tamoxifen (TAM, an anticancer drug). 7,12-Dimethylbenz[a]anthracene (DMBA), a complete carcinogen, also causes neutrophil infiltration, H2O2, HMdU, and 8-OHdG formation in the skin of topically treated mice. Hence, inflammation with its attendant oxidative stress and oxidative DNA base modification may be common denominators of tumor promotional processes. Therefore, inhibiting those processes with antioxidants and other chemopreventive agents might protect against cancer development. We find that DMBA induces the formation of an inflammatory cytokine IL-1a in mouse skin akin to tumor promoter TPA. IL-1a initially works to counteract the initiation step but, once tumors are formed, it contributes to the tumor promotion and progression to carcinomas in DMBA-treated mouse skin. More recently, we have been studying the mechanism of human cell transformation by arsenite or by estradiol and searching for agents that can prevent cell transformation and/or kill the already transformed cells. We find that CAPE (see above), even when used at very low doses, can prevent As-induced human cell transformation and counteract massive down-regulation of inflammatory cytokines and of the transcription factor NF-kB1, as well as induce apoptosis in As-transformed cells or cancerous breast epithelial cells, without any effect on normal cells. Genes and their protein products involved in the cell transformation are being determined. Currently, we are using a nude mouse model to establish the effects of CAPE on the growth of human breast cancer cells as xenografts. We find that CAPE inhibits growth of breast cancer ER(+) as well as ER(-) cells as tumors at doses that are very low (nmol amounts of CAPE/-mouse/day). CAPE causes down-regulation of cell proliferation, pro-survival, and cell cycle-related genes, growth factors, oncogenes, inflammatory cytokines and chemokines, pro-angiogenic factors and certain transcriotion factors. Recently, we found that cancer stem cells isolated from aggressive human triple-negative breast cancer cells respond to treatment with CAPE, including suppression of growth in soft agar and decreasing CD44 levels by >10-fold, thus, creating less malignant phenotype. All these properties could be useful in inhibiting growth, metastatsis, angiogenesis, and possibly recurrance of breast cancer in patients. In addition, we discovered that people elaborate autoantibodies (aAb) recognizing HMdU when it is coupled to bovine serum albumin. Anti-HMdU aAb levels are significantly elevated in the sera of women with a family history of cancer and those who may develop cancer (breast, colorectal, lung and others). People occupationally exposed to carcinogenic metals also exhibit elevated anti-HMdU aAb, which could be used to identify people at risk for developing cancer. In summary, our investigations are focused on: 1) studies on the mechanisms of cell transformation and carcinogenesis, with the emphasis on the role of inflammatory factors; 2) establishing whether EGCG, CAPE, and TAM suppress DMBA-mediated carcinogenesis; 3) elucidating mechanism(s) by which preventive agents exert their protective action; 4) conducting molecular epidemiology studies to prove that anti-HMdU aAb can provide a measure of cancer risk; and 5) evaluating whether CAPE could have clinical applications in preventing and/or treating human breast cancer.

Research Interests

Inflammation, Oxidants and Oxidative DNA Damage in Carcinogenesis, Cell Transformation and Carcinogenesis, Cancer stem cells, Biomarkers of Cancer Susceptibility, Prevention.

Increased endogenous oxidative levels correlate to increased iron in melanocytes
Pelle, E.; Huang, X.; Zhang, Q.; Pernodet, N.; Yarosh, D. B.; Frenkel, K.
2014-05-19; 0022-202x,Journal of investigative dermatology - id: 997182, year: 2014

Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes
Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna
2015-02-22; 1525-7886,Journal of cosmetic science - id: 1465872, year: 2014 Journal Article

Propolis and its active component, Caffeic acid phenethyl ester (CAPE), modulate breast cancer therapeutic targets via an epigenetically mediated mechanism of action
Omene, C; Kalac, M; Wu, J; Marchi, E; Frenkel, K; O'Connor, O A
2014-01-07; 1948-5956,Journal of cancer science & therapy - id: 712982, year: 2013

Menopause increases the iron storage protein ferritin in skin
Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi
2013-07-22; 1525-7886,Journal of cosmetic science - id: 438832, year: 2013 Journal Article

Caffeic Acid Phenethyl Ester (CAPE) derived from propolis, a honeybee product, inhibits growth of breast cancer stem cells
Omene CO; Wu J; Frenkel K
2012-02-05; 1573-0646,Investigational new drugs - id: 146298, year: 2012