Back to Search
Start Over
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.
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.
- Source :
-
Toxicology letters [Toxicol Lett] 2016 Aug 22; Vol. 257, pp. 84-96. Date of Electronic Publication: 2016 Jun 03. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents, Phytogenic isolation & purification
Cell Cycle Checkpoints drug effects
Cell Proliferation drug effects
Cell Shape drug effects
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
Dose-Response Relationship, Drug
HCT116 Cells
Humans
Inhibitory Concentration 50
Phytotherapy
Plants, Medicinal
Resins, Plant isolation & purification
Sesquiterpenes isolation & purification
Signal Transduction drug effects
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Apoptosis Regulatory Proteins metabolism
Colorectal Neoplasms drug therapy
Magnoliopsida chemistry
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Resins, Plant pharmacology
Sesquiterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 257
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 27268964
- Full Text :
- https://doi.org/10.1016/j.toxlet.2016.05.027