title: Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression.
abstract: The epidermal growth factor receptor (EGFR) is an oncogene frequently overexpressed in breast cancer (BC), and its overexpression has been associated with poor prognosis and drug resistance. EGFR is therefore a rational target for BC therapy development. This study demonstrated that a graviola fruit extract (GFE) significantly downregulated EGFR gene expression and inhibited the growth of BC cells and xenografts. GFE selectively inhibited the growth of EGFR-overexpressing human BC (MDA-MB-468) cells (IC(50) = 4.8 μg/ml) but had no effect on nontumorigenic human breast epithelial cells (MCF-10A). GFE significantly downregulated EGFR mRNA expression, arrested cell cycle in the G0/G1 phase, and induced apoptosis in MDA-MB-468 cells. In the mouse xenograft model, a 5-wk dietary treatment of GFE (200 mg/kg diet) significantly reduced the protein expression of EGFR, p-EGFR, and p-ERK in MDA-MB-468 tumors by 56%, 54%, and 32.5%, respectively. Overall, dietary GFE inhibited tumor growth, as measured by wet weight, by 32% (P < 0.01). These data showed that dietary GFE induced significant growth inhibition of MDA-MB-468 cells in vitro and in vivo through a mechanism involving the EGFR/ERK signaling pathway, suggesting that GFE may have a protective effect for women against EGFR-overexpressing BC.
authors.affiliation: Department of Food Science and Technology, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Dai
authors.forename: Shelly
authors.initials: S
authors.lastname: Hogan
authors.forename: Eva M
authors.initials: EM
authors.lastname: Schmelz
authors.forename: Young H
authors.initials: YH
authors.lastname: Ju
authors.forename: Corene
authors.initials: C
authors.lastname: Canning
authors.forename: Kequan
authors.initials: K
authors.lastname: Zhou
mesh_terms: D000818:Animals; D031041:Annona / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors