title: Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines.
abstract: Cervical cancer represents the largest cause of mortality in women worldwide. In our previous report, we have shown how alpha-linolenic acid (ALA), an omega-3 fatty acid, regulated the growth of cervical cancer cells. The present study aimed to explore mechanistic details for the anticancer activity of ALA in cervical cancer cell lines, SiHa and HeLa. ALA significantly modulated the growth kinetics of the cells and reduced cell migration with concomitant decrease in the expression of VEGF, MMP-2, and MMP-9 proteins. Besides this, ALA significantly decreased the expression of phosphorylated p38, pERK1/2, c-JUN, NFκB, and COX2, proteins. Most importantly, ALA reduced the expression of HPV onco-proteins E6 and E7, resulting into restoration of expression of tumor suppressor proteins, p53 and Rb. These results suggested that ALA could be explored for its therapeutic potential in cervical cancer.
authors.affiliation: Interactive Research School for Health Affairs (IRSHA), BharatiVidyapeeth University, Katraj-Dhankawadi, Pune-Satara Road, Pune, 411043, Maharashtra, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Deshpande
authors.affiliation: Interactive Research School for Health Affairs (IRSHA), BharatiVidyapeeth University, Katraj-Dhankawadi, Pune-Satara Road, Pune, 411043, Maharashtra, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Mansara
authors.affiliation: Interactive Research School for Health Affairs (IRSHA), BharatiVidyapeeth University, Katraj-Dhankawadi, Pune-Satara Road, Pune, 411043, Maharashtra, India. ruchika.kaulghanekar@gmail.com.
authors.forename: Ruchika
authors.initials: R
authors.lastname: Kaul-Ghanekar
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000378:metabolism / Q000502:physiology; D052161:Human papillomavirus 18 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C059731:oncogene protein E7, Human papillomavirus type 16; D017962:alpha-Linolenic Acid; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Alpha-linolenic acid; Cervical cancer; HPV oncoproteins; NF-κB