A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1 - read online free

Sep 21, 2026

Cannabinoid-type I (CB1) receptor signaling controls cell fate through apoptosis versus survival, and dysregulated CB1 activity can drive ceramide accumulation in fast-growing cancers. This study examines ovarian cancer cells (PA1) expressing CB1 and evaluates a non-psychoactive fatty acid ester (bis(palmitoleic acid) ester of a glycerol, C2) isolated from the marine snail Conus inscriptus. The compound induces two acute ceramide pools, triggers G0/G1 arrest, and promotes apoptosis via C16:0 and C18:0 ceramides. It is not genotoxic in non-cancerous CHO cells and shows no observable neurobehavioral changes in zebrafish models, supporting safety alongside anticancer activity.

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CategoryResearch & Report

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molecules Article A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1 Christina Sathyanathan Vijayaraghavan 1, Lakshmi Sundaram Raman 2, Shanmugapriya Surenderan 3, Harpreet Kaur 4, Mohanapriya Dandapani Chinambedu 4, Sadras Panchatcharam Thyagarajan 5 and Mary Elizabeth Gnanambal Krishnan 1, * Citation: Vijayaraghavan, C.S.; Raman, L.S.; Surenderan, S.; Kaur, H.; Chinambedu, M.D.; Thyagarajan, S.P.; Gnanambal Krishnan, M.E. A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1 . Molecules 2024, 29, 1737 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29081737 Academic Editor: Changsheng Zhang Received: 11 December 2023 Revised: 6 February 2024 Accepted: 21 February 2024 Published: 11 April 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 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; [christy.sathya@gmail.com](christy.sathya@gmail.com) 2 Faculty of Pharmacy, SRI RAMACHANDRA Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600116, Tamil Nadu, India; [sundaram@sriramachandra.edu.in](sundaram@sriramachandra.edu.in) 3 Whizbang Bioresearch Private Limited, Porur, Chennai 600077, Tamil Nadu, India; [whizbangbioresearch@gmail.com](whizbangbioresearch@gmail.com) 4 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; [pre.singh@gmail.com](pre.singh@gmail.com) (H.K.); [mohanapriya@sriramachandra.edu.in](mohanapriya@sriramachandra.edu.in) (M.D.C.) 5 Distinguished Professor and Advisor to Chancellor, Vellore Institute of technology (VIT), Vellore Campus, Tiruvalam Rd, Katpadi, Vellore 632014, Tamil Nadu, India; [profspt@gmail.com](profspt@gmail.com) * Correspondence: [drelizabethrajesh@sriramachandra.edu.in](drelizabethrajesh@sriramachandra.edu.in) Abstract: 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 ef

FAQs

What is the main signaling target investigated in the study?

The study focuses on the cannabinoid receptor type 1 (CB1), examining how CB1 signaling relates to apoptosis versus survival through ceramide accumulation.

How does the marine-derived compound affect cancer cells?

The compound increases intracellular ceramides (C16:0 and C18:0), induces G0/G1 arrest, and kills the PA1 ovarian cancer cells by apoptosis.

What evidence is provided for safety and lack of psychotropic effects?

The compound does not induce micronuclei formation in non-cancerous CHO cells and produces no observable neurobehavioral changes in zebrafish treatment groups, supporting non-toxicity and absence of psychotropic effects.

Sep 21, 2026

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