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Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-ß and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment.
Shalev, Nurit; Kendall, Michelle; Kumar, Navin; Tiwari, Sudeep; Anil, Seegehalli M; Hauschner, Hagit; Swamy, Savvemala G; Doron-Faingenboim, Adi; Belausov, Eduard; Kendall, Bruce E; Koltai, Hinanit.
Afiliación
  • Shalev N; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
  • Kendall M; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Kumar N; Canna Onc Research, Santa Barbara, CA, United States.
  • Tiwari S; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Anil SM; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Hauschner H; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Swamy SG; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
  • Doron-Faingenboim A; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Belausov E; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Kendall BE; Volcani Center, Agriculture Research Organization, Institute of Plant Science, Rishon LeZion, Israel.
  • Koltai H; Canna Onc Research, Santa Barbara, CA, United States.
Front Genet ; 15: 1333964, 2024.
Article en En | MEDLINE | ID: mdl-38322025
ABSTRACT

Introduction:

Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction ('F7') and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3. Materials and

methods:

Gene expression profiles were determined by RNA sequencing and quantitative PCR. Microscopy was used to determine actin arrangement, a scratch assay to determine cell migration and flow cytometry to determine apoptosis, cell cycle and aldehyde dehydrogenase (ALDH) activity. Western blotting was used to determine protein levels.

Results:

Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-ß/Activin and MAPK were enriched with genes differentially expressed by niraparib and/or F7 treatments in both cell lines. Niraparib + F7 treatment led to cell cycle arrest and endoplasmic reticulum (ER) stress, inhibited cell migration, reduced the % of ALDH positive cells in the population and enhanced PARP1 cleavage.

Conclusion:

The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Genet Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Genet Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza