title: Ginger extract adjuvant to doxorubicin in mammary carcinoma: study of some molecular mechanisms.
abstract: OBJECTIVE
  The present study aimed to investigate the molecular mechanisms underlying the anticancer properties of ginger extract (GE) in mice bearing solid Ehrlich carcinoma (SEC) and to evaluate the use of GE in combination with doxorubicin (DOX) as a complementary therapy against SEC.
  
  
  METHODS
  SEC was induced in 60 female mice. Mice were divided into four equal groups: SEC, GE, DOX and GE + DOX. GE (100 mg/kg orally day after day) and DOX (4 mg/kg i.p. for 4 cycles every 5 days) were given to mice starting on day 12 of inoculation. On the 28th day, blood samples were collected, mice were scarified, tumor volume was measured, and tumor tissues were excised.
  
  
  RESULTS
  The anti-cancer effect of GE was mediated by activation of adenosine monophosphate protein kinase (AMPK) and down-regulation of cyclin D1 gene expression. GE also showed pro-apoptotic properties as evidenced by elevation of the P53 and suppression of nuclear factor-kappa B (NF-κB) content in tumor tissue. Co-administration of GE alongside DOX markedly increased survival rate, decreased tumor volume, and increased the level of phosphorylated AMPK (PAMPK) and improved related pathways compared to DOX group. In addition, the histopathological results demonstrated enhanced apoptosis and absence of multinucleated cells in tumor tissue of GE + DOX group.
  
  
  CONCLUSIONS
  AMPK pathway and cyclin D1 gene expression could be a molecular therapeutic target for the anticancer effect of GE in mice bearing SEC. Combining GE and DOX revealed a greater efficacy as anticancer therapeutic regimen.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Tanta University, 31527, Tanta, Egypt.
authors.forename: Nahla E
authors.initials: NE
authors.lastname: El-Ashmawy
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Tanta University, 31527, Tanta, Egypt.
authors.forename: Naglaa F
authors.initials: NF
authors.lastname: Khedr
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Tanta University, 31527, Tanta, Egypt.
authors.forename: Hoda A
authors.initials: HA
authors.lastname: El-Bahrawy
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Tanta University, 31527, Tanta, Egypt. hend_elsayed_2010@yahoo.com.
authors.forename: Hend E
authors.initials: HE
authors.lastname: Abo Mansour
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004317:Doxorubicin / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020939:Zingiber officinale / Q000737:chemistry*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009336:Necrosis; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D027343:Rhizome / Q000737:chemistry; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C530106:Ccnd1 protein, rat; D009363:Neoplasm Proteins; D010936:Plant Extracts; D019938:Cyclin D1; D004317:Doxorubicin; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Cyclin D1; Doxorubicin; Ginger; Mammary carcinoma; Solid Ehrlich carcinoma