2. Academic Validation
  3. The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation

The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation

  • Neurochem Res. 2026 Jan 14;51(1):43. doi: 10.1007/s11064-025-04654-x.
Ana Laura Torres-Román 1,  Alette Ortega-Gómez 2 3,  Carolina Y Reyes-Soto 1,  Omar Emiliano Aparicio-Trejo 4,  Belén Cuevas-López 4,  Fernando E García-Arroyo 4,  Erika Ruíz-García 5,  Juan A Matus-Santos 6,  Beatriz Ferrer 7,  Michael Aschner 7,  Gustavo Jardón 8,  Tessy López-Goerne 8,  Anayansi Molina-Hernández 9,  Juan Carlos Tenorio-Monterrubio 10,  Abel Santamaría 11 12
Affiliations

Affiliations

  • 1 Programa de Posgrado (Doctorado) en Ciencias Biológicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
  • 2 Subdirección de Oncología y Hematología, Instituto Nacional de Cancerología, 14080, Mexico City, Mexico. [email protected].
  • 3 Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico. [email protected].
  • 4 Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, 14080, Mexico City, Mexico.
  • 5 Dirección de Docencia, Instituto Nacional deCancerología, 14080, Mexico City, Mexico.
  • 6 International Oncologic Center (COI), 04700, Mexico City, Mexico.
  • 7 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • 8 Laboratorio de Nanotecnología y Nanomedicina, Departamento de Atención a la Salud, Universidad Autónoma Metropolitana-Xochimilco, 04960, Mexico City, Mexico.
  • 9 Subdirección de Investigación Médica, Instituto Nacional de Perinatología, 11000, Mexico City, Mexico.
  • 10 Centro Oncológico de Oriente (COORI), 56363, Chimalhuacan, Estado de México, Mexico.
  • 11 Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico. [email protected].
  • 12 Laboratorio de Nanotecnología y Nanomedicina, Departamento de Atención a la Salud, Universidad Autónoma Metropolitana-Xochimilco, 04960, Mexico City, Mexico. [email protected].
PMID: 41533230 DOI: 10.1007/s11064-025-04654-x
Abstract

The endocannabinoid anandamide (AEA) and the related metabolite oleamide (ODA) have been demonstrated to possess anti-proliferative properties by recruiting apoptotic mechanisms in glioblastoma cells; however, the role of receptors Other than the canonical cannabinoid receptors in their pattern of anti-proliferative mechanisms has been poorly investigated. Here, we evaluated the role of mitochondrial function and PPAR-γ membrane receptors in the anti-proliferative mechanisms induced by AEA and ODA in the glioblastoma cell lines C6 and RG2. Cell viability and lipid peroxidation assessments in both cell lines showed antiproliferative and pro-oxidant effects of the tested cannabinoids, respectively, compared to primary astrocyte cultures used as a non-tumor negative control. AEA and ODA also reduced mitochondrial membrane potential in C6, but not in RG2 cells, while impairing mitochondrial Complex I activity in C6. The PPAR-γ receptor antagonist GW9662 showed differential effects on the AEA- and ODA-induced loss of cell viability in both cell lines, as well as in mitochondrial membrane potential. The ontogenetic origin and metabolic differences between RG2 and C6 cell lines may establish differential responses evoked by endogenous cannabinoids and PPAR-γ receptor modulation. Combined, our results demonstrate that AEA and ODA modulate mitochondrial function in glioblastoma cells by inhibiting the activity of mitochondrial Complex 1, which in turn increases markers of oxidative damage and interferes with glioblastoma proliferation.

Keywords

Antitumor activity; Brain cancer; Endocannabinoid system; Mitochondrial metabolism; Oxidative stress; PPAR-γ.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.98%, PPARγ Antagonist