| Autor: |
Vijayaraghavan CS; Department of Biotechnology, Faculty of Biomedical Sciences and Technology, SRI Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India., Raman LS; Faculty of Pharmacy, SRI RAMACHANDRA Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India., Surenderan S; Whizbang Bioresearch Private Limited, Porur, Chennai 600077, Tamil Nadu, India., Kaur H; Department of Human Genetics, Faculty of Biomedical Sciences and Technology, SRI Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India., Chinambedu MD; Department of Human Genetics, Faculty of Biomedical Sciences and Technology, SRI Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India., Thyagarajan SP; Distinguished Professor and Advisor to Chancellor, Vellore Institute of technology (VIT), Vellore Campus, Tiruvalam Rd, Katpadi, Vellore 632014, Tamil Nadu, India., Gnanambal Krishnan ME; Department of Biotechnology, Faculty of Biomedical Sciences and Technology, SRI Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India. |
| Abstrakt: |
The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol ( C2 ). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects. |
