Natural phytochemicals as testable therapeutic alternatives for HER‑2‑enriched breast cancer (Review)
Affiliations: Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645‑1559, USA
- Published online on: July 17, 2020 https://doi.org/10.3892/wasj.2020.60
Copyright: © Telang
et al. This is an open access article distributed under the
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The human epidermal growth factor receptor‑2 (HER‑2)‑enriched molecular subtype of breast cancer responds to HER‑2 targeted and/or to endocrine therapy, depending on the presence of functional hormone receptors. These long‑term therapeutic options are associated with systemic toxicity and acquired drug resistance. Resistance to conventional and targeted chemo‑endocrine therapy leads to the emergence of drug‑resistant cancer stem cells that promote therapy‑resistant disease progression. Relatively non‑toxic natural phytochemicals may provide testable alternatives to therapy‑resistant breast cancer. The present review summarizes data on the following: i) Growth inhibitory efficacy of mechanistically distinct natural phytochemicals in a preclinical model for HER‑2‑enriched breast cancer; ii) drug‑resistant stem cell model for HER‑2‑enriched breast cancer; and iii) proof of concept for efficacy of natural phytochemicals as testable alternatives against drug‑resistant cancer stem cells. Relative to the non‑tumorigenic human mammary epithelial 184‑B5 cells, HER‑2 expressing tumorigenic 184‑B5/HER cells (HER‑2‑enriched breast cancer model) exhibit hyper‑proliferation and increased anchorage independent colony formation. Resistance to lapatinib, a small molecule inhibitor of EGFR and HER‑2, provides the LAP‑R phenotype that exhibits increased tumor spheroid formation and an upregulated expression of the stem cell markers, CD44, NANOG and OCT‑4. Select bioactive natural phytochemicals, such as cruciferous glucosinolate, tea polyphenol, soy isoflavone and rosemary terpenoid at their respective maximum cytostatic concentrations exert anti‑proliferative and pro‑apoptotic effects on parental 184‑B5/HER cells and downregulate the phosphorylation of HER‑2. The expression of stem cell markers in the LAP‑R phenotype is effectively inhibited by a bioactive terpenoid. Collectively, these data validate an experimental approach to identify efficacious natural phytochemicals as testable therapeutic alternatives for chemo‑endocrine therapy resistant breast cancer.