Isoledene from Mesua ferrea oleo-gum resin induces apoptosis in HCT 116 cells through ROS-mediated modulation of multiple proteins in the apoptotic pathways: A mechanistic study
| Autor: | Koji Kono, Seyedeh Fatemeh Jafari, Mohammed Oday Ezzat, Aman Shah Abdul Majid, Amin Malik Shah Abdul Majid, Muhammad Asif, Sven H. Petersen, Shazmin Kithur Mohamed, Chern Ein Oon, Armaghan Shafaei |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apoptosis Toxicology Inhibitory Concentration 50 Magnoliopsida 03 medical and health sciences 0302 clinical medicine Survivin Humans Cell Shape Cell Proliferation Plants Medicinal Dose-Response Relationship Drug biology Cell growth Cytochrome c Cell Cycle Checkpoints General Medicine HCT116 Cells Antineoplastic Agents Phytogenic XIAP Cell biology Oxidative Stress 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research DNA fragmentation Apoptosis Regulatory Proteins Colorectal Neoplasms Reactive Oxygen Species Sesquiterpenes Resins Plant Phytotherapy Signal Transduction |
| Zdroj: | Toxicology Letters. 257:84-96 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2016.05.027 |
| Popis: | Colorectal cancer (CRC) is one of the most common human malignant tumors worldwide. Arising from the transformation of epithelial cells in the colon and/or rectum into malignant cells, the foundation of CRC pathogenesis lies in the progressive accumulation of mutations in oncogenes and tumor-suppressor genes, such as KRAS and APC. Resistance to apoptosis is one of the key mechanisms in the development of CRC as it is for any other kind of cancer. Natural products have been shown to induce the expression of apoptosis regulators that are blocked in cancer cells. In the present study, a series of in vitro assays were employed to study the apoptosis-inducing attributes of Isoledene rich sub-fraction (IR-SF) collected from the oleo-gum resin of M. ferrea. Data obtained, showed that IR-SF inhibited cell proliferation and induced typical apoptotic changes in the overall morphology of all the CRC cell lines tested. Fluorescent staining assays revealed characteristic nuclear condensation, and marked decrease in mitochondrial outer membrane potential in the treated cells. In addition, an increment in the levels of ROS, caspase-8, -9 and -3 was observed. Proteomic analysis revealed that IR-SF up-regulated the expression of pro-apoptotic proteins, i.e., Bid, Bim and cytochrome c. Cytochrome c in turn activated caspases cascade resulting in the induction of apoptosis. Moreover, IR-SF significantly down-regulated Bcl-2, Bcl-w, survivin, xIAP and HSPs pro-survival proteins and induced DNA fragmentation and G0/G1-phase arrest in HCT 116 cells. Chemical characterization of IR-SF by GC-MS and HPLC methods identified Isoledene as one of the major compounds. Altogether, results of the present study demonstrate that IR-SF may induce apoptosis in human colorectal carcinoma cells through activation of ROS-mediated apoptotic pathways. |
| Databáze: | OpenAIRE |
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