The chemotherapeutic effect of β-2-himachalen-6-ol in chemically induced skin tumorigenesis
| Autor: | Wassim N. Shebaby, Mohamad Mroueh, Robin I. Taleb, Carole Dagher, Kikki Bodman-Smith, Mirvat El-Sibai, Costantine F. Daher, Hamid E. Daaboul |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Skin Neoplasms Carcinogenesis Cell Survival MAP Kinase Signaling System 9 10-Dimethyl-1 2-benzanthracene DMBA Pharmacology Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Viability assay Protein kinase B Cisplatin Mice Inbred BALB C Dose-Response Relationship Drug Chemistry General Medicine Antineoplastic Agents Phytogenic Treatment Outcome 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Toxicity Female Liver function Sesquiterpenes medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 103:443-452 |
| ISSN: | 0753-3322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect