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Inhibition of Growth Factor Action as an Approach to Cancer Chemotherapy
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
The selectivity of all three of these compounds is unknown; orobol, for example, has been reported to also inhibit dopa decarboxylase and histidine decarboxylase.94 Orobol inhibits the growth of sarcoma virus-transformed rat kidney cells and erbstatin inhibits the growth of human epidermoid carcinoma A431 cells and IMC-carcinoma cells.93 It is not known if inhibition of tyrosine protein kinase is related to growth inhibition or even if any tyrosine protein kinase is effectively inhibited in intact cells by these compounds.
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Genistein (Figure 12(c)), a potent bioactive isoflavone present in red clover (Trifolium pratense) and soybean (Glycine max), has been known as a hormone replacement alternative in menopause due to its preferential estrogen receptor β estrogenic effect (Hajirahimkhan et al. 2013). Genistein can be oxidized by CYP1A2 to the catechol orobol which yields an ortho-quinone after two-electron oxidation (Figure 12(c)) (Bolton and Dunlap 2017). Genistein protected against acetaminophen-induced injury in human hepatic cell lines by promoting acetaminophen glucuronidation via activation of the Keap1/Nrf2/ARE pathway and induction of UGT enzymes (Fan et al. 2013; Yuan-Jing et al. 2016). Orobol induced oxidative damage to DNA through metal-catalyzed Fenton chemistry whereas genistein had no effect (Murata et al. 2004). These data suggest that genistein can be carcinogenic via ROS formation and oxidative stress upon autoxidation of orobol to orobol ortho-quinone. However, it’s unlikely that such a mode of action presents a cancer risk at low dietary intake when antioxidant protection is not overwhelmed (Klein and King 2007).