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has been cited by the following article:

• TITLE: Differential Anticancer Effect of an Apple Extract (Applephenon®), Polyphenols and Isoflavones on Normal Human Keratinocytes and Epidermoid Cancer Cells

  AUTHORS: John J. Wille, Mark A. Berhow, Jong Y. Park

  KEYWORDS: ApplephenonTM (AP-SH Grade), Cytotoxicity, Epicatechin, Epidermal Keratinocytes Epidermoid Cancer Cell Lines (A431, HaCaT, HeLa), Genistein, Polyphenols

  JOURNAL NAME: Journal of Cancer Therapy, Vol.10 No.6, June 30, 2019

  ABSTRACT: Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer cell lines. Our HPLC studies demonstrated a high content of phenolic compounds (>65%), including catechin, epicatechin, caffeic acid and phloretin as well as polyphenols such as proanthocyanidins. Applephenon® demonstrated a greater cytotoxic effect against HeLa, A431 cancer cell lines and HaCaT, an immortalized keratinocyte cell line than serum-free cultures of proliferating normal human keratinocytes (NHK). Proliferation of NHK was inhibited at concentrations above 0.0013% while concentrations above 0.005% were cytotoxic. By contrast, Applephenon® solutions above 0.00025% killed each of the cancer cell lines. Treated cells displayed increased intercellular separation and evidence of keratinizing stratification. We also tested the effect of epicatechin, and two isoflavonoids, genistein and daidzein, on cancer cell lines. Hela cells were more sensitive to epicatechin and genistein inhibition of cell growth and cytotoxicity than were NHK. Daidzein at these concentrations had little effect on cancer cells. These results indicate that Applephenon® and some of its phenolic components have selective anticancer activity.