The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis
β-2-himachalen-6-ol (HC), a novel sesquiterpene derived from Lebanese wild carrot, was shown to possess a remarkable anticancer activity. The present study investigates the in vitro anticancer activity of HC and its effect on papillomas induced using a DMBA/TPA skin carcinogenesis mouse model. HaCaT...
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2018
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| Online Access: | http://hdl.handle.net/10725/11398 https://doi.org/10.1016/j.biopha.2018.04.027 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0753332217350837 |
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| _version_ | 1864513488717611008 |
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| author | Daaboul, Hamid E. |
| author2 | Dagher, Carole Taleb, Robin I. Bodman-Smith, Kikki Shebaby, Wassim N. El-Sibai, Mirvat Mroueh, Mohamad A. Daher, Costantine F. |
| author2_role | author author author author author author author |
| author_facet | Daaboul, Hamid E. Dagher, Carole Taleb, Robin I. Bodman-Smith, Kikki Shebaby, Wassim N. El-Sibai, Mirvat Mroueh, Mohamad A. Daher, Costantine F. |
| author_role | author |
| dc.creator.none.fl_str_mv | Daaboul, Hamid E. Dagher, Carole Taleb, Robin I. Bodman-Smith, Kikki Shebaby, Wassim N. El-Sibai, Mirvat Mroueh, Mohamad A. Daher, Costantine F. |
| dc.date.none.fl_str_mv | 2018 2019-10-08T13:29:29Z 2019-10-08T13:29:29Z 2019-10-08 |
| dc.identifier.none.fl_str_mv | 1950-6007 http://hdl.handle.net/10725/11398 https://doi.org/10.1016/j.biopha.2018.04.027 Daaboul, H. E., Dagher, C., Taleb, R. I., Bodman-Smith, K., Shebaby, W. N., El-Sibai, M., ... & Daher, C. F. (2018). The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis. Biomedicine & Pharmacotherapy, 103, 443-452. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0753332217350837 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Biomedicine & Pharmacotherapy |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | β-2-himachalen-6-ol (HC), a novel sesquiterpene derived from Lebanese wild carrot, was shown to possess a remarkable anticancer activity. The present study investigates the in vitro anticancer activity of HC and its effect on papillomas induced using a DMBA/TPA skin carcinogenesis mouse model. HaCaT-ras II-4 epidermal squamous cell viability was assessed using WST-1 kit. Cell cycle was analyzed by flow cytometry, and pro/anti-apoptotic proteins were measured using western blot. Mice papillomas were induced by DMBA and promoted with TPA for 18 weeks. At week 12, animals were divided into four groups: HC topically treated (5%Top), HC intraperitoneally treated (25 mg/kg; HC25), Cisplatin treated (2.5 mg/kg), and control (DMSO treated). Papilloma yield, volume, histology, and mice weight and liver function were assessed. HC treatment decreased significantly cell survival (IC50 = 7 and IC90 = 40 μg/ml) and increased significantly cells undergoing late apoptosis and necrosis. It also significantly decreased the levels of pro-caspase-3, p53, Bcl-2, p-Erk/Erk and p-Akt/Akt and increased p21 and Bax proteins. Treatment with HC25, HC5%Top or Cisplatin showed a significant decrease in papilloma yield and volume. Only Cisplatin treatment caused a significant decrease in body weight and increase in serum ALT. In conclusion, β-2-himachalen-6-ol induced significant tumor shrinkage, an effect partly mediated via promoting apoptosis through inhibition of the MAPK/ERK and PI3K/AKT pathways, with no significant toxicity to laboratory mice. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_29e996130b5b4c1ca50f84615bf52263 |
| identifier_str_mv | 1950-6007 Daaboul, H. E., Dagher, C., Taleb, R. I., Bodman-Smith, K., Shebaby, W. N., El-Sibai, M., ... & Daher, C. F. (2018). The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis. Biomedicine & Pharmacotherapy, 103, 443-452. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/11398 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesisDaaboul, Hamid E.Dagher, CaroleTaleb, Robin I.Bodman-Smith, KikkiShebaby, Wassim N.El-Sibai, MirvatMroueh, Mohamad A.Daher, Costantine F.β-2-himachalen-6-ol (HC), a novel sesquiterpene derived from Lebanese wild carrot, was shown to possess a remarkable anticancer activity. The present study investigates the in vitro anticancer activity of HC and its effect on papillomas induced using a DMBA/TPA skin carcinogenesis mouse model. HaCaT-ras II-4 epidermal squamous cell viability was assessed using WST-1 kit. Cell cycle was analyzed by flow cytometry, and pro/anti-apoptotic proteins were measured using western blot. Mice papillomas were induced by DMBA and promoted with TPA for 18 weeks. At week 12, animals were divided into four groups: HC topically treated (5%Top), HC intraperitoneally treated (25 mg/kg; HC25), Cisplatin treated (2.5 mg/kg), and control (DMSO treated). Papilloma yield, volume, histology, and mice weight and liver function were assessed. HC treatment decreased significantly cell survival (IC50 = 7 and IC90 = 40 μg/ml) and increased significantly cells undergoing late apoptosis and necrosis. It also significantly decreased the levels of pro-caspase-3, p53, Bcl-2, p-Erk/Erk and p-Akt/Akt and increased p21 and Bax proteins. Treatment with HC25, HC5%Top or Cisplatin showed a significant decrease in papilloma yield and volume. Only Cisplatin treatment caused a significant decrease in body weight and increase in serum ALT. In conclusion, β-2-himachalen-6-ol induced significant tumor shrinkage, an effect partly mediated via promoting apoptosis through inhibition of the MAPK/ERK and PI3K/AKT pathways, with no significant toxicity to laboratory mice.PublishedN/A2019-10-08T13:29:29Z2019-10-08T13:29:29Z20182019-10-08Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1950-6007http://hdl.handle.net/10725/11398https://doi.org/10.1016/j.biopha.2018.04.027Daaboul, H. E., Dagher, C., Taleb, R. I., Bodman-Smith, K., Shebaby, W. N., El-Sibai, M., ... & Daher, C. F. (2018). The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis. Biomedicine & Pharmacotherapy, 103, 443-452.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.sciencedirect.com/science/article/pii/S0753332217350837enBiomedicine & Pharmacotherapyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/113982024-01-30T13:15:42Z |
| spellingShingle | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis Daaboul, Hamid E. |
| status_str | publishedVersion |
| title | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| title_full | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| title_fullStr | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| title_full_unstemmed | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| title_short | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| title_sort | The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis |
| url | http://hdl.handle.net/10725/11398 https://doi.org/10.1016/j.biopha.2018.04.027 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S0753332217350837 |