{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:32:50Z","timestamp":1791930770598,"version":"4.3.4"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The therapeutic potential of\n                      <jats:italic>Cannabis sativa<\/jats:italic>\n                      has attracted growing interest in oncology. Its diverse phytochemicals, including cannabinoids, flavonoids, and terpenes, interact with oncogenic signaling pathways and the endocannabinoid system influencing tumour progression and therapeutic responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This review critically evaluates the molecular mechanisms by which\n                      <jats:italic>Cannabis sativa<\/jats:italic>\n                      phytochemicals modulate cancer pathways, with emphasis on apoptosis, oxidative stress regulation, autophagy, angiogenesis, and metastasis. It also explores synergistic and additive interactions among cannabinoids and flavonoids, highlighting their translational relevance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Findings<\/jats:title>\n                    <jats:p>Cannabinoids such as \u03949-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG) exhibit pathway-specific effects, including induction of apoptosis, modulation of oxidative stress, and inhibition of angiogenesis. Flavonoids such as cannflavin A, genistein, daidzein, hesperetin, and naringenin exhibit selective cytotoxicity across bladder, breast, melanoma, and pancreatic cancers, often sparing normal tissue. Importantly, phytochemical interactions are not uniformly synergistic; while combinations such as THC and CBD amplify apoptotic signaling, others act additively or antagonistically. Clinical formulations such as Nabiximols provide translational evidence of cannabinoid synergy, although outcomes remain context-dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The disconnect between preclinical efficacy and clinical outcomes underscores critical gaps in dosing strategies, patient selection, and combination regimens. Future research should prioritize mechanistic studies, rational phytochemical combinations, and innovative drug delivery systems. Taken together,\n                      <jats:italic>Cannabis sativa<\/jats:italic>\n                      phytochemicals emerge as promising molecular entities with the potential to reshape integrative oncology, provided their therapeutic promise is matched with rigorous, evidence-based evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1768210","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:21:14Z","timestamp":1782195674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cannabis sativa phytochemicals in cancer therapy: molecular mechanisms and therapeutic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Rosemary","family":"Montle","sequence":"first","affiliation":[{"name":"Institute of Chemical and Biotechnology, Vaal University of Technology","place":["Sebokeng, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garland K.","family":"More","sequence":"additional","affiliation":[{"name":"College of Agriculture and Environmental Sciences, University of South Africa","place":["Johannesburg, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samkeliso","family":"Takaidza","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Vaal University of Technology","place":["Vanderbijlpark, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyana","family":"Mtunzi","sequence":"additional","affiliation":[{"name":"Institute of Chemical and Biotechnology, Vaal University of Technology","place":["Sebokeng, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.3390\/biom9110735","article-title":"Role of reactive oxygen species in cancer progression: molecular mechanisms and recent advancements","volume":"9","author":"Aggarwal","year":"2019","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s43450-025-00620-4","article-title":"Phytochemicals in cancer therapy: modulating cell cycle, angiogenesis, and epithelial-mesenchymal transition","volume":"35","author":"Ahmad","year":"2025","journal-title":"Rev. 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