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Although olaparib works mainly in BRCA-mutated tumors, its effect in BRCA-wild type (BRCA-wt) cancers is limited. This study tested whether cannabidiol (CBD) enhances BRCA-wt breast cancer responses to PARP inhibition using 2D mechanistic assays and 3D spheroid models in multiple cell lines. Combined OLAP and CBD increased cytotoxicity and apoptosis, induced G2/M arrest, and modulated DNA damage response and cell-cycle genes, supporting CBD as a potential combination strategy.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cannabidiol-potentiates-olaparib-induced-cytotoxicity-through-cell-cycle-arrest-and-dna-damage-modulation-in-breast-cancer-cells/353124/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cannabidiol-potentiates-olaparib-induced-cytotoxicity-through-cell-cycle-arrest-and-dna-damage-modulation-in-breast-cancer-cells/353124.png","ImageObject",300,407,{"name":92,"@type":93},"Jasmine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the main research goal of the study?","Question",{"text":113,"@type":114},"To determine whether cannabidiol (CBD) can enhance the response of BRCA-wild type breast cancer cells to olaparib-based PARP inhibition.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which cell models were used to evaluate the effects?",{"text":118,"@type":114},"The study tested olaparib and CBD alone and in combination in MDA-MB-231 and MCF-7 cell lines, including HCC-70 cells, using 2D analyses and 3D spheroid models.",{"name":120,"@type":111,"acceptedAnswer":121},"How did the combination treatment affect cancer cells?",{"text":122,"@type":114},"The combined OLAP and CBD treatment increased cytotoxicity, promoted apoptosis, and induced G2/M phase arrest, with supporting changes in DNA damage response and cell-cycle gene expression.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353124,1790174612,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336478487870,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Cannabidiol potentiates olaparib-induced cytotoxicity through cell cycle arrest and DNA damage modulation in breast cancer cells  \nCansın Deniz1 · BüşraYüksel1 · Emre Cebeci1 · Fikrettin Şahin1  \nReceived: 3 February 2026 / Accepted: 13 April 2026 / Published online: 28 April 2026 © The Author(s) 2026  \nAbstract  \nTriple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature and limited treatment options, while therapeutic resistance in estrogen receptor-positive (ER+) breast cancer continues to limit treatment efficacy. Although olaparib is primarily effective in BRCA-mutated cancers, its activity in BRCA-wild type (BRCA-wt) tumors is limited. Therefore, this study aimed to investigate whether cannabidiol (CBD) can enhance the response of BRCA-wt breast cancer cells to PARP inhibition. The effects of olaparib (OLAP) and CBD, alone and in combination, were evaluated in MDA-MB-231 (TNBC) and MCF-7 (ER+) cell lines using comprehensive two-dimensional (2D) mechanistic analyses and three-dimensional (3D) spheroid models, including HCC-70 cells to extend TNBC validation. The results demonstrate that combined OLAP and CBD treatment enhanced cytotoxic effects compared to single treatments, with more pronounced responses observed in 3D spheroid models, particularly in TNBC models. Flow cytometry and caspase 3/7 assays indicated increased apoptosis and G2/M phase arrest following combination treatment. Gene expression analysis revealed downregulation of key DNA damage response and cell cycle-related genes (ATM, ATR, BRCA1/2, RAD51, and CDK1/2/4/6), supporting a role for cell cycle arrest and DNA damage modulation in mediating these effects. Functional assays showed reduced colony formation and migratory capacity, although these effects may reflect both cytotoxic and cytostatic responses under the selected experimental conditions. Overall, these findings suggest that CBD may enhance the efficacy of olaparib in BRCA-wt breast cancer models and highlight its potential as a combinational therapeutic strategy in breast cancer treatment.  \nKeywords TNBC · Breast Cancer · Olaparib · CBD  \nIntroduction  \nCancer is a complex disease characterized by diverse subtypes, multifactorial etiology, and profound physiological alterations that lead to malignant tumor formation [1] . Among women, breast cancer is the most commonly diagnosed malignancy. Although it predominantly affects women over the age of 50, breast cancer can also occur in younger individuals and, less frequently, in men [2] . When detected at an early stage, breast cancer is often curable; however, invasive and advanced forms remain challenging  \n􀀍 Fikrettin Şahin[fsahin@yeditepe.edu.tr](fsahin@yeditepe.edu.tr)  \n1 Faculty of Engineering and Natural Sciences, Genetics and Bioengineering Department, Yeditepe University,  \n34755 Kayışdağı, Istanbul, Turkey  \nto treat. Disease staging is determined based on tumor size, lymph node involvement, and the presence of distant metastasis [3, 4] . While early-stage cancers generally respond well to treatment, advanced-stage disease is associated with an increased risk of metastasis and requires more complex therapeutic strategies [5, 6] .  \nDespite advances in targeted therapies, breast cancer treatment remains a significant clinical challenge due to drug resistance, tumor heterogeneity, and the adverse side effects associated with conventional therapies [7] . In this context, natural compounds are increasingly investigated as alternative or complementary therapeutic options [8] . These bioactive substances, derived primarily from plants or other natural sources, have demonstrated anticancer properties, including reduced toxicity, inhibition of metastasis, and induction of apoptosis [9] . Consequently, the integration of natural compounds into cancer treatment strategies  \nhas gained growing interest in both preclinical and clinical research settings [10] .  \nCannabinoids are bioactive compounds originatin","cbCaijaaaBB5WwA0","https://ap.wps.com/l/cbCaijaaaBB5WwA0","pdf",1748882,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"What was the main research goal of the study?\",\"answer\":\"To determine whether cannabidiol (CBD) can enhance the response of BRCA-wild type breast cancer cells to olaparib-based PARP inhibition.\"},{\"question\":\"Which cell models were used to evaluate the effects?\",\"answer\":\"The study tested olaparib and CBD alone and in combination in MDA-MB-231 and MCF-7 cell lines, including HCC-70 cells, using 2D analyses and 3D spheroid models.\"},{\"question\":\"How did the combination treatment affect cancer cells?\",\"answer\":\"The combined OLAP and CBD treatment increased cytotoxicity, promoted apoptosis, and induced G2/M phase arrest, with supporting changes in DNA damage response and cell-cycle gene expression.\"}]","Cannabidiol potentiates olaparib-induced cytotoxicity through cell cycle arrest and DNA damage modulation in breast cancer cells | PDF",1790103153,33]