Apple compound phloretin reduces TN cell growth and migration

Posted: April 23, 2017

Study:	The apple polyphenol phloretin inhibits breast cancer cell migration and proliferation via inhibition of signals by type 2 glucose transporter Cite Wu K, Ho C, Chen Z, Chen L, Whang-Peng J, Lin T, et al. The apple polyphenol phloretin inhibits breast cancer cell migration and proliferation via inhibition of signals by type 2 glucose transporter. Journal of Food and Drug Analysis. The Journal of Food and Drug Analysis (JFDA), Food and Drug Administration, Taiwan (TFDA); 2018; 26:221-231 10.1016/j.jfda.2017.03.009
Publication:	Journal of Food and Drug Analysis, April 2017

Study:

The apple polyphenol phloretin inhibits breast cancer cell migration and proliferation via inhibition of signals by type 2 glucose transporter Cite

Wu K, Ho C, Chen Z, Chen L, Whang-Peng J, Lin T, et al. The apple polyphenol phloretin inhibits breast cancer cell migration and proliferation via inhibition of signals by type 2 glucose transporter. Journal of Food and Drug Analysis. The Journal of Food and Drug Analysis (JFDA), Food and Drug Administration, Taiwan (TFDA); 2018; 26:221-231 10.1016/j.jfda.2017.03.009

Publication:

Journal of Food and Drug Analysis, April 2017

Apple compound reduces triple negative breast cancer growth

Phloretin, a type of flavonoid found primarily in apples, has been shown to inhibit the growth of various types of cancer cells, including colon, leukemia, lung, liver and melanoma, in addition to breast cancer. Phloretin also enhances the sensitivity of cancer cells to Taxol and cisplatin chemotherapy. In fact, phloretin has been shown to reverse multidrug resistance in cancer cells.

The development of multidrug resistance is a major cause of immediate or eventual chemotherapy failure. Now a new study has reported that phloretin inhibits triple negative (ER-/PR-/HER2-) breast cancer cell growth and migration by interfering with glucose transport into the cells.

Latest research finds phloretin inhibits TN cancer in cell and animal studies

The study referenced above was designed to investigate whether using the apple polyphenol phloretin to inhibit glucose transporters could be an effective treatment for triple negative breast cancer. Glucose transporters (GLUTs) are proteins that help cells import glucose by a type of diffusion. Since most cancer cells have a preference for high glucose conditions, glucose transporters are targets for cancer therapy.

To conduct the study, the authors used phloretin as an antagonist of GLUT2 function in MDA-MB-231 triple negative breast cancer cells. Phloretin treatment (at 10-150 μM, for 24 hours) was found to inhibit cell growth and arrest the cell cycle in a p53 mutant-dependent manner. p53 is a tumor suppressor protein whose activation normally results either in cell death or DNA repair. However, p53 mutations can endow p53 with new functions.

Phloretin treatment was also found to significantly reduce the migratory activity of triple negative cells.

The authors also used a mouse model of triple negative breast cancer (BALB/c nude mice bearing MDA-MB-231 tumor xenografts) to test the effects of phloretin. Phloretin was confirmed to have anti-tumorigenic effects in the mice in a six-week experiment. This was accompanied by expected changes in the mouse tumor tissue, including an increase in p53.

The authors conclude that phloretin could potentially suppress triple negative breast cancer cell growth and metastasis through inhibition of GLUT2.

Please see our article on triple negative diet for more information.

Selected breast cancer studies

Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study Cite
Farvid MS, Chen WY, Michels KB, Cho E, Willett WC, Eliassen AH. Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study. BMJ. BMJ; 2016;:i2343 10.1136/bmj.i2343
Evaluation of antioxidative and antitumor activities of extracted flavonoids from Pink Lady apples in human colon and breast cancer cell lines Cite
Yang S, Zhang H, Yang X, Zhu Y, Zhang M. Evaluation of antioxidative and antitumor activities of extracted flavonoids from Pink Lady apples in human colon and breast cancer cell lines. Food & Function. Royal Society of Chemistry (RSC); 2015; 6:3789-3798 10.1039/c5fo00570a
Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar Cite
Schiavano GF, De Santi M, Brandi G, Fanelli M, Bucchini A, Giamperi L, et al. Inhibition of Breast Cancer Cell Proliferation and In Vitro Tumorigenesis by a New Red Apple Cultivar. PLOS ONE. Public Library of Science (PLoS); 2015; 10:e0135840 10.1371/journal.pone.0135840
Phloretin Induces Apoptosis in H-Ras MCF10A Human Breast Tumor Cells through the Activation of p53 via JNK and p38 Mitogen-Activated Protein Kinase Signaling Cite
Kim M, Kwon JY, Kang NJ, Lee KW, Lee HJ. Phloretin Induces Apoptosis in H-Ras MCF10A Human Breast Tumor Cells through the Activation of p53 via JNK and p38 Mitogen-Activated Protein Kinase Signaling. Annals of the New York Academy of Sciences. Wiley; 2009; 1171:479-483 10.1111/j.1749-6632.2009.04692.x
Apple polyphenol phloretin potentiates the anticancer actions of paclitaxel through induction of apoptosis in human hep G2 cells Cite
Yang K, Tsai C, Wang Y, Wei P, Lee C, Chen J, et al. Apple polyphenol phloretin potentiates the anticancer actions of paclitaxel through induction of apoptosis in human hep G2 cells. Molecular Carcinogenesis. Wiley; 2009; 48:420-431 10.1002/mc.20480
Effects of the Flavonoids Biochanin A, Morin, Phloretin, and Silymarin on P-Glycoprotein-Mediated Transport Cite
Zhang S, Morris ME. Effects of the Flavonoids Biochanin A, Morin, Phloretin, and Silymarin on P-Glycoprotein-Mediated Transport. Journal of Pharmacology and Experimental Therapeutics. American Society for Pharmacology & Experimental Therapeutics (ASPET); 2002; 304:1258-1267 10.1124/jpet.102.044412

Latest research finds phloretin inhibits TN cancer in cell and animal studies

Selected breast cancer studies

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