title: Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms.
abstract: Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention.
  
  
  
  This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC).
  
  
  
  Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC+5-FU, SEC+apigenin, SEC+ 5-FU+apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated by ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis.
  
  
  
  5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group.
  
  
  
  The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice.
authors.affiliation: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, 3111, Egypt. Electronic address: hanaahibishy@hotmail.com.
authors.forename: Hanaa H
authors.initials: HH
authors.lastname: Gaballah
authors.affiliation: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, 3111, Egypt.
authors.forename: Rasha A
authors.initials: RA
authors.lastname: Gaber
authors.affiliation: Histopathology Department, Faculty of Medicine, Tanta University, Tanta, 3111, Egypt.
authors.forename: Darin A
authors.initials: DA
authors.lastname: Mohamed
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D047310:Apigenin / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000964:Antimetabolites, Antineoplastic; D019394:Ki-67 Antigen; C579094:Mcl1 protein, mouse; C498355:Mki67 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D047310:Apigenin; D048670:MAP Kinase Kinase 4; D005472:Fluorouracil
keywords: 5-FU; Apigenin; Apoptosis; Autophay; Ehrlich tumor; JNK activity