title: Methyl jasmonate reduces the survival of cervical cancer cells and downregulates HPV E6 and E7, and survivin.
abstract: The present study further investigated the mode of action of methyl jasmonate (MJ) in different cervical cancer cell lines. We show that in addition to the short term cytotoxicity, MJ effectively reduced the survival of cervical cancer cells (clonogenicity assays). MJ induced apoptosis in all cervical cancer cells. In some cell lines, MJ caused elevation of the mitochondrial superoxide anion, notably, in HeLa and CaSki. Changes in the expression of p53 and bax were variable, yet, downregulation of survivin was common to all cervical cancer cells. MJ significantly reduced the levels of the human papillomavirus (HPV) E6 and E7 proteins without alteration of the mRNA levels. Moreover, ectopic expression of E6, E7 or both in cervical cancer cells that lack HPV (C33A), did not alter significantly their response to MJ. Our studies point to MJ as an effective anticancer agent against a variety of cervical cancer cells acting through shared and different pathways to induce cell death regardless of the presence of HPV.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Milrot
authors.forename: Anna
authors.initials: A
authors.lastname: Jackman
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kniazhanski
authors.forename: Pinhas
authors.initials: P
authors.lastname: Gonen
authors.forename: Eliezer
authors.initials: E
authors.lastname: Flescher
authors.forename: Levana
authors.initials: L
authors.lastname: Sherman
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000187:drug effects* / Q000378:metabolism; D054883:Oxylipins / Q000494:pharmacology*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000187:drug effects* / Q000378:metabolism; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D003517:Cyclopentanes; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D051034:Inhibitor of Apoptosis Proteins; D009856:Oncogene Proteins, Viral; D054883:Oxylipins; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D000077022:Survivin; C072239:methyl jasmonate