Differential anticancer effect of an apple extract (Applephenon®), polyphenols and isoflavones on normal human keratinocytes and epidermoid cancer cells

Authors: WILLE, JOHN - Bioplast Medical, Llc; Berhow, Mark; PARK, JONG - H Lee Moffitt Cancer Center

Submitted to: Journal of Cancer Therapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/27/2019
Publication Date: 6/30/2019
Citation: Wille, J.J., Berhow, M.A., Park, J.Y. 2019. Differential anticancer effect of an apple extract (Applephenon®), polyphenols and isoflavones on normal human keratinocytes and epidermoid cancer cells. Journal of Cancer Therapy. 10:476-493.
DOI: https://doi.org/10.4236/jct.2019.106040

Interpretive Summary: A purified extract prepared from green apples was examined for its effects on cultures of normal human skin cells and several human skin cancer cell lines. Our studies showed a high content of phenolic compounds (>65%), as well as polyphenols. This extract demonstrated a greater toxic effect against three cancer cell lines than against normal human cultured skin cells. Treated cells displayed increased intercellular separation and evidence of normal skin cell development. We also tested the effect of four plant phenolics found in the apple extract on cancer cell lines. Cancer cells were more sensitive to inhibition of cell growth and cell death with three of four compounds tested than were normal cells. These results indicate that this apple extract and some of its phenolic components have selective anticancer activity.

Technical 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.