Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

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...

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Bibliographic Details
Published in:	Frontiers in genetics Vol. 15; p. 1333964
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 2024
Subjects:	apoptosis cannabis cell cycle Genetics mesenchymal phenotype ovarian cancer phytocannabinoids cell cycle ovarian cancer phytocannabinoids Hippo/Wnt pathway cannabis apoptosis mesenchymal phenotype endoplasmic reticulum stress
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Summary:	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. 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. Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-β/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. The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Anamaria Brozovic, Rudjer Boskovic Institute, Croatia Masoumeh Tavakoli-Yaraki, Iran University of Medical Sciences, Iran Deceased Reviewed by: Maja Sabol, Ruđer Bošković Institute, Croatia
ISSN:	1664-8021 1664-8021
DOI:	10.3389/fgene.2024.1333964