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
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...
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| Veröffentlicht in: | Tumor biology 2016-03, Vol.37 (3), p.3295-3305 |
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| creator | Deshpande, Rashmi Mansara, Prakash Kaul-Ghanekar, Ruchika |
| description | 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. |
| doi_str_mv | 10.1007/s13277-015-4170-z |
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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.</description><subject>Acids</subject><subject>alpha-Linolenic Acid - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cervical cancer</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>HeLa Cells</subject><subject>Host-Pathogen Interactions</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - metabolism</subject><subject>Human papillomavirus 16 - physiology</subject><subject>Human papillomavirus 18 - metabolism</subject><subject>Human papillomavirus 18 - physiology</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Kinases</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Oncogene Proteins, Viral - metabolism</subject><subject>Original Article</subject><subject>Papillomavirus E7 Proteins - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Proteins</subject><subject>Repressor Proteins - metabolism</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Uterine Cervical Neoplasms - virology</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNksFu1DAQhiNERUvbB-CCLHHhYtaOnTg-rlbbFqmICkGv0cSZ3bhk7WAnpe3r8WJ4u0tVISFx8nj8zT8znsmyN5x94IypWeQiV4oyXlDJFaMPL7IjLnNBmajYy2QzzqjMK3GYvY7xhiVQ6_JVdpiXUjIm9VH2a94PHdDeOt-js4aAsS0JuJ56GDGShb_LZ9fL87PZp_kV-W4dRCQDjN1PuCfgWtKiCZickYwdErwbAsZovSN-RS6urol3xg_Bj2hdJMtytlQJDH5adylLHH2AcU8PhXhU_NI8l7GOdNMGHDEYbq2BnhhwyU73viepbown2cEK-oin-_M4-3a2_Lq4oJefzz8u5pfUSMVHqhjyBnT6AQYFVC2UoIFVSomqkI1RommVURx5gZVplRQcVljKRhTYCqMbcZy93-mmfn5Mqfh6Y-O2DHDop1hzpaXUWqjqP9BKKqm5lgl99xd646fgUiNbSmgh5aMg31Em-BgDruoh2A2E-5qzersM9W4Z6jTjersM9UOKebtXnpoNtk8Rf6afgHwHxPTk1hiepf6n6m86U8E3</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Deshpande, Rashmi</creator><creator>Mansara, Prakash</creator><creator>Kaul-Ghanekar, Ruchika</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>7U9</scope></search><sort><creationdate>20160301</creationdate><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</title><author>Deshpande, Rashmi ; Mansara, Prakash ; Kaul-Ghanekar, Ruchika</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-70e1ba99960a5a8da6a9a08773854bc73bd7c71e15e8cd7431afe64b35ed3c9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acids</topic><topic>alpha-Linolenic Acid - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cervical cancer</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>HeLa Cells</topic><topic>Host-Pathogen Interactions</topic><topic>Human papillomavirus</topic><topic>Human papillomavirus 16 - metabolism</topic><topic>Human papillomavirus 16 - physiology</topic><topic>Human papillomavirus 18 - metabolism</topic><topic>Human papillomavirus 18 - physiology</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Kinases</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Oncogene Proteins, Viral - metabolism</topic><topic>Original Article</topic><topic>Papillomavirus E7 Proteins - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Proteins</topic><topic>Repressor Proteins - metabolism</topic><topic>Retinoblastoma Protein - metabolism</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Uterine Cervical Neoplasms - virology</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Deshpande, Rashmi</creatorcontrib><creatorcontrib>Mansara, Prakash</creatorcontrib><creatorcontrib>Kaul-Ghanekar, Ruchika</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deshpande, Rashmi</au><au>Mansara, Prakash</au><au>Kaul-Ghanekar, Ruchika</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>37</volume><issue>3</issue><spage>3295</spage><epage>3305</epage><pages>3295-3305</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><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.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26440049</pmid><doi>10.1007/s13277-015-4170-z</doi><tpages>11</tpages></addata></record> |
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| subjects | Acids alpha-Linolenic Acid - pharmacology Biomedical and Life Sciences Biomedicine Cancer Research Cell Line, Tumor Cell Proliferation - drug effects Cervical cancer Cyclooxygenase 2 - metabolism DNA-Binding Proteins - metabolism Dose-Response Relationship, Drug Female HeLa Cells Host-Pathogen Interactions Human papillomavirus Human papillomavirus 16 - metabolism Human papillomavirus 16 - physiology Human papillomavirus 18 - metabolism Human papillomavirus 18 - physiology Humans Immunoblotting Kinases MAP Kinase Signaling System - drug effects Mitogen-Activated Protein Kinases - metabolism NF-kappa B - metabolism Oncogene Proteins, Viral - metabolism Original Article Papillomavirus E7 Proteins - metabolism Phosphorylation - drug effects Proteins Repressor Proteins - metabolism Retinoblastoma Protein - metabolism Tumor Suppressor Protein p53 - metabolism Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - pathology Uterine Cervical Neoplasms - virology Vascular Endothelial Growth Factor A - metabolism |
| 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 |
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