Wild carrot pentane-based fractions suppress proliferation of human HaCaT keratinocytes and protect against chemically-induced skin cancer

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dc.contributor.author Shebaby, Wassim N.
dc.contributor.author Mroueh, Mohamad A.
dc.contributor.author Boukamp, Petra
dc.contributor.author Bodman-Smith, Kikki
dc.contributor.author Ishac Taleb, Robin
dc.contributor.author El-Sibai, Mirvat
dc.contributor.author Daher, Costantine F.
dc.date.accessioned 2017-03-14T10:05:36Z
dc.date.available 2017-03-14T10:05:36Z
dc.date.copyright 2017 en_US
dc.date.issued 2017-03-14
dc.identifier.issn 1472-6882 en_US
dc.identifier.uri http://hdl.handle.net/10725/5365
dc.description.abstract Background Previous studies in our laboratory showed that the Lebanese Daucus carota ssp. carota (wild carrot) oil extract possesses in vitro and in vivo anticancer activities. The present study aims to examine the cytotoxic effect of Daucus carota oil fractions on human epidermal keratinocytes and evaluate the chemopreventive activity of the pentane diethyl ether fraction on DMBA/TPA induced skin carcinogenesis in mice. Methods Wild carrot oil extract was chromatographed to yield four fractions (F1, 100% pentane; F2, 50:50 pentane:diethyl ether; F3, 100% diethyl ether; F4 93:7 chloroform:methanol). The cytotoxic effect of fractions (10, 25, 50 and 100 μg/mL) was tested on human epidermal keratinocytes (non-tumorigenic HaCaT cells and tumorigenic HaCaT-ras variants) using WST a ssay. Cell cycle phase distribution of tumorigenic HaCaT-ras variants was determined by flow cytometry post-treatment with F2 fraction. Apoptosis related proteins were also assessed using western blot. The antitumor activity of F2 fraction was also evaluated using a DMBA/TPA induced skin carcinoma in Balb/c mice. Results All fractions exhibited significant cytotoxicity, with HaCaT cells being 2.4–3 times less sensitive than HaCaT-ras A5 (benign tumorigenic), and HaCaT-ras II4 (malignant) cells. GC-MS analysis revealed the presence of a major compound (around 60%) in the pentane/diethylether fraction (F2), identified as 2-himachalen-6-ol. Treatment of HaCaT-ras A5 and HaCaT-ras II4 cells with F2 fraction resulted in the accumulation of cells in the sub-G1 apoptotic phase and decreased the population of cells in the S and G2/M phases. Additionally, F2 fraction treatment caused an up-regulation of the expression of pro-apoptotic (Bax) and down-regulation of the expression of anti-apoptotic (Bcl2) proteins. A decrease in the phosphorylation of AKT and ERK was also observed. Intraperitoneal treatment with F2 fraction (50 or 200 mg/kg) in the DMBA/TPA skin carcinogenesis mouse model showed a significant inhibition of papilloma incidence (mice with papilloma), yield (number of papilloma/mouse) and volume (tumor relative size) at weeks 15, 18 and 21. Conclusion The present data reveal that F2 fraction has a remarkable antitumor activity against DMBA/TPA-induced skin carcinogenesis, an effect that may be mediated through inhibition of the MAPK/ERK and PI3K/AKT pathways. en_US
dc.language.iso en en_US
dc.title Wild carrot pentane-based fractions suppress proliferation of human HaCaT keratinocytes and protect against chemically-induced skin cancer en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school N/A en_US
dc.author.school SOP
dc.author.school SAS en_US
dc.author.idnumber 199190130 en_US
dc.author.idnumber 200901968 en_US
dc.author.idnumber 200703859
dc.author.idnumber 199590020
dc.author.department Natural Sciences
dc.description.embargo N/A en_US
dc.relation.journal BMC Complementary and Alternative Medicine en_US
dc.journal.volume 17 en_US
dc.journal.issue 36 en_US
dc.article.pages 36
dc.keywords Daucus carota en_US
dc.keywords Wild carrot en_US
dc.keywords HaCaT en_US
dc.keywords TPA/DMBA skin cancer en_US
dc.identifier.doi http://dx.doi.org/10.1186/s12906-016-1531-0 en_US
dc.identifier.ctation Shebaby, W. N., Mroueh, M. A., Boukamp, P., RI, R. I. T., Bodman-Smith, K., El-Sibai, M., & Daher, C. F. (2017). Wild carrot pentane-based fractions suppress proliferation of human HaCaT keratinocytes and protect against chemically-induced skin cancer. BMC Complementary and Alternative Medicine, 17(1), 36. en_US
dc.author.email mmroueh@lau.edu.lb en_US
dc.author.email robin.taleb@lau.edu.lb en_US
dc.author.email mirvat.elsibai@lau.edu.lb
dc.author.email cdaher@lau.edu.lb
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-016-1531-0 en_US
dc.orcid.id https://orcid.org/0000-0002-8275-7263 en_US
dc.orcid.id https://orcid.org/0000-0001-8033-6951 en_US
dc.orcid.id https://orcid.org/0000-0003-4084-6759 en_US
dc.author.affiliation Lebanese American University en_US

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