{"id":2734,"date":"2020-04-12T12:42:57","date_gmt":"2020-04-12T10:42:57","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2734"},"modified":"2021-09-05T12:44:29","modified_gmt":"2021-09-05T10:44:29","slug":"differential-effects-of-thymoquinone-on-lysophosphatidic-acid-induced-oncogenic-pathways-in-ovarian-cancer-cells","status":"publish","type":"post","link":"https:\/\/www.isidorolab.com\/public\/index.php\/2020\/04\/12\/differential-effects-of-thymoquinone-on-lysophosphatidic-acid-induced-oncogenic-pathways-in-ovarian-cancer-cells\/","title":{"rendered":"Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2734\" class=\"elementor elementor-2734\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-35fc09e8 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"35fc09e8\" data-element_type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-463f896b\" data-id=\"463f896b\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-151f28 elementor-widget elementor-widget-text-editor\" data-id=\"151f28\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ha+JH&amp;cauthor_id=32670815\">Ji Hee Ha<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Jayaraman+M&amp;cauthor_id=32670815\">Muralidharan Jayaraman<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Radhakrishnan+R&amp;cauthor_id=32670815\">Rangasudhagar Radhakrishnan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Gomathinayagam+R&amp;cauthor_id=32670815\">Rohini Gomathinayagam<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yan+M&amp;cauthor_id=32670815\">Mingda Yan<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Song+YS&amp;cauthor_id=32670815\">Yong Sang Song<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-3\"> 3 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=32670815\">Ciro Isidoro<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-4\"> 4 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+DN&amp;cauthor_id=32670815\">Danny N Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32670815\/#affiliation-2\"> 2<\/a><\/sup><\/p>\n<p>\u00a0<\/p>\n\n<h3 class=\"wp-block-heading\">Affiliations<\/h3>\n\n<p><sup>1<\/sup> Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.<\/p>\n<p><sup>2<\/sup> Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.<\/p>\n<p><sup>3<\/sup> Cancer Research Institute, Seoul National University, College of Medicine, Seoul, 151-921, South Korea.<\/p>\n<p><sup>4<\/sup> Universit\u00e0 del Piemonte Orientale, Novara, Italy.<\/p>\n<p>\u00a0<\/p>\n\n<p>PMID: <strong>32670815<\/strong><\/p>\n<p>PMCID: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/pmc7340879\/\" target=\"_blank\" rel=\"noreferrer noopener\">PMC7340879<\/a><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.1016\/j.jtcme.2020.04.001\" target=\"_blank\" rel=\"noreferrer noopener\">10.1016\/j.jtcme.2020.04.001<\/a><\/p>\n\n<p>J Tradit Complement Med. 2020 Apr 12;10(3):207-216. doi: 10.1016\/j.jtcme.2020.04.001. eCollection 2020 May.<\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n<p>Thymoquinone, a therapeutic phytochemical derived from Nigella sativa, has been shown to have a potent anticancer activity. However, it has been identified that the tumor microenvironment (TME) can attenuate the anticancer effects of thymoquinone (TQ) in ovarian cancer. Lysophosphatidic acid (LPA), a lipid growth factor present in high concentration in the TME of ovarian cancer, has been shown to regulate multiple oncogenic pathways in ovarian cancer. Taking account of the crucial role of LPA in the genesis and progression of ovarian cancer, the present study is focused on assessing the efficacy of TQ in inhibiting LPA-stimulated oncogenic pathways in ovarian cancer cells. Our results indicate that TQ is unable to attenuate LPA-stimulated proliferation or metabolic reprogramming in ovarian cancer cells. However, TQ potently inhibits the basal as well as LPA-stimulated migratory responses of the ovarian cancer cells. Furthermore, TQ abrogates the invasive migration of ovarian cancer cells induced by G\u03b1i2, through which LPA stimulates cell migration. TQ also attenuates the activation of JNK, Src, and FAK, the downstream signaling nodes of LPA-LPAR-G\u03b1i2 signaling pathway. In addition to establishing the differential effects of TQ in ovarian cancer cells, our results unravel the antitherapeutic role of LPA in the ovarian cancer TME could override the inhibitory effects of TQ on cell proliferation and metabolic reprogramming of ovarian cancer cells. More importantly, the concomitant finding that TQ could still sustain its inhibitory effect on LPA-stimulated invasive cell migration, points to its potential use as a response-specific therapeutic agent in ovarian cancer.<\/p>\n<p>\u00a0<\/p>\n<p>\u00a0<\/p>\n\n<p><strong>Keywords:<\/strong> Anticancer; LPA; Ovarian cancer; Phytochemical; Thymoquinone.<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t<div style='text-align:center' class='yasr-auto-insert-visitor'><!--Yasr Visitor Votes Shortcode--><div id='yasr_visitor_votes_e769610aa66e1' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2734\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-e769610aa66e1'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-e769610aa66e1'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2734'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='c484e8bd77'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-e769610aa66e1\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2734\"\r\n                                   id=\"yasr-stats-dashicon-e769610aa66e1\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-e769610aa66e1\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-e769610aa66e1\">0<\/span>  Average: <span id=\"yasr-vv-average-container-e769610aa66e1\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-e769610aa66e1' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-e769610aa66e1' class='yasr-vv-bottom-container'><\/div><\/div><!--End Yasr Visitor Votes Shortcode--><\/div>","protected":false},"excerpt":{"rendered":"<p>Ji Hee Ha\u00a0 1 \u00a0 2 ,\u00a0Muralidharan Jayaraman\u00a0 1 \u00a0 2 ,\u00a0Rangasudhagar Radhakrishnan\u00a0 1 ,\u00a0Rohini Gomathinayagam\u00a0 1 \u00a0 2 ,\u00a0Mingda Yan\u00a0 1 ,\u00a0Yong Sang Song\u00a0 3 ,\u00a0Ciro Isidoro\u00a0 4 ,\u00a0Danny N Dhanasekaran\u00a0 1 \u00a0 2 \u00a0 Affiliations 1 Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. 2 Department&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[62],"class_list":["post-2734","post","type-post","status-publish","format-standard","hentry","category-paper","tag-ovarian-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - 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