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A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to

Christina Sathyanathan Vijayaraghavan1, Lakshmi Sundaram Raman2, Shanmugapriya Surenderan3

  • 1Department 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.

Molecules (Basel, Switzerland)
|April 27, 2024
PubMed

Insights

A novel marine compound, C2, acts as a potent CB1 agonist, inducing apoptosis in ovarian cancer cells. This non-toxic compound shows no psychotropic effects in zebrafish, suggesting potential therapeutic applications.

Area of Science:

  • Pharmacology
  • Marine Biotechnology
  • Cancer Research

Background:

  • The cannabinoid type I (CB1) receptor plays a dual role in cell fate, influencing both survival and apoptosis.
  • Elevated CB1 receptor expression in cancers can lead to ceramide accumulation, supporting rapid tumor growth.
  • Paradoxically, sustained CB1 activation can trigger a secondary ceramide peak, inducing cancer cell death.

Purpose of the Study:

  • To investigate the effects of a novel marine compound (C2) on ovarian cancer cells.
  • To determine if C2 acts as a CB1 agonist and induces apoptosis.
  • To assess the safety and potential psychotropic effects of C2.

Main Methods:

  • Ovarian cancer cells (PA1) were treated with compound C2, isolated from *Conus inscriptus*.
  • CB1 receptor expression and intracellular ceramide levels (C:16, C:18) were measured.
  • Genotoxicity was assessed using micronuclei formation in Chinese hamster ovarian (CHO) cells.
  • Neurobehavioral changes were evaluated in zebrafish models.

Main Results:

  • Compound C2, a bis(palmitoleic acid) ester of glycerol, increased CB1 receptor expression threefold in PA1 cells.
  • C2 induced two acute ceramide pools, leading to G0/G1 arrest and apoptosis.
  • Intracellular ceramides C:16 and C:18 increased 7-fold and 10-fold, respectively, confirming C2 as a potent CB1 agonist.
  • C2 was not genotoxic in CHO cells and showed no observable neurobehavioral changes in zebrafish.

Conclusions:

  • The marine compound C2 effectively triggers the CB1 pathway, inducing apoptosis in ovarian cancer cells.
  • C2 demonstrates a dual ceramide-inducing mechanism, leading to cancer cell death.
  • C2 is non-toxic, non-genotoxic, and lacks psychotropic effects, indicating its safety for potential therapeutic use.
Keywords:
FAAH1MD simulationapoptosiscannabinoid receptor 1 (CB1)ceramideovarian cancerzebrafish models

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