Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways

LAUR Repository

Show simple item record

dc.contributor.author Daaboul, Hamid E.
dc.contributor.author Daher, Costantine F.
dc.contributor.author Bodman-Smith, Kikki
dc.contributor.author Taleb, Robin I.
dc.contributor.author Shehaby, Wassim N.
dc.contributor.author Boulos, Joelle
dc.contributor.author Dagher, Carole
dc.contributor.author Mroueh, Mohamad A.
dc.contributor.author El-Sibai, Mirvat
dc.date.accessioned 2017-12-15T11:07:58Z
dc.date.available 2017-12-15T11:07:58Z
dc.date.copyright 2017 en_US
dc.date.issued 2017-12-15
dc.identifier.issn 1872-7786 en_US
dc.identifier.uri http://hdl.handle.net/10725/6798
dc.description.abstract Previous studies in our laboratory showed that Daucus carota oil extract (DCOE) possesses in vitro and in vivo anticancer activities. Chemical analysis of DCOE led to the isolation of β-2-himachalen-6-ol (HC) which exhibited potent anticancer activity against colon, breast, brain and skin cancer cells. The present study investigates the anticancer activity of HC against SW1116 colon cancer cell lines, and evaluates its effect in a 1,2-dimethylhydrazine (DMH) colon carcinogenesis black6 mice model. The SW1116 colon cancer cell line was treated with HC (1, 5, 10 and 25 μg/ml) and cell viability was evaluated with WST 1 assay kit. Cell cycle analysis was carried out by flow cytometry, and pro/anti-apoptotic proteins were measured using western blot. The effect of intraperitoneal (IP) treatment with HC (10, 25 and 50 μg/ml) in mice was assessed using the DMH colon carcinogenesis model with Cisplatin (2.5 μg/kg; IP) as a positive control. Blood samples were collected for assessment of liver toxicity and colon tumor incidence and size were studied histologically. HC showed a dose-dependent decrease in cell survival with an IC50 of 18 and 14.5 μg/ml after 24 and 48 h respectively. Flow cytometry analysis revealed that 10 μg/ml HC increased the number of cells undergoing necrosis (18.05%) and late apoptosis (15.66%). At HC 25 μg/ml more cells shifted toward necrosis (58.01%) and late apoptosis (30.47%). Western blot analysis revealed a significant decrease in p-Erk, p-Akt, pro-caspase-3 and Bcl-2 and an increase in p53, p21, Bax and PARP proteins. Mice treatment (IP) with HC caused a significant decrease in tumor incidence and size. Similar effects were observed with cisplatin treatment. In conclusion, HC treatment (low dose) induced cell cycle arrest and promoted apoptosis via inhibition of the MAPK/ERK and PI3K/AKT pathways. HC treatment also had antitumor effect in vivo with no significant toxicity to laboratory mice. en_US
dc.language.iso en en_US
dc.title Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOP en_US
dc.author.school SAS en_US
dc.author.idnumber 199190130 en_US
dc.author.idnumber 200901968 en_US
dc.author.idnumber 199590020 en_US
dc.author.idnumber 200703859 en_US
dc.author.department Pharmaceutical Sciences Department en_US
dc.description.embargo N/A en_US
dc.relation.journal Chemico-Biological Interactions en_US
dc.journal.volume 275 en_US
dc.article.pages 162-170 en_US
dc.keywords Daucus carota en_US
dc.keywords β-2-Himachalen-6-ol en_US
dc.keywords Colon cancer en_US
dc.keywords PI3K en_US
dc.keywords ERK en_US
dc.identifier.doi https://doi.org/10.1016/j.cbi.2017.08.003 en_US
dc.identifier.ctation Daaboul, H. E., Daher, C. F., Bodman-Smith, K., Taleb, R. I., Shebaby, W. N., Boulos, J., ... & El-Sibai, M. (2017). Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways. Chemico-biological interactions, 275, 162-170. en_US
dc.author.email cdaher@lau.edu.lb en_US
dc.author.email robin.taleb@lau.edu.lbmirvat.elsibai@lau.edu.lb en_US
dc.author.email mmroueh@lau.edu.lb en_US
dc.author.email robin.taleb@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.sciencedirect.com/science/article/pii/S0009279717302685 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.orcid.id https://orcid.org/0000-0002-8275-7263 en_US
dc.author.affiliation Lebanese American University en_US

Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search LAUR

Advanced Search


My Account