Targeting Gastrointestinal Cancers with Cannabidiol: Mechanisms, Challenges, and Therapeutic Implications

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209–49.

Google Scholar 

Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020;396(10251):635–48.

Article  CAS  Google Scholar 

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–91.

Article  PubMed  Google Scholar 

Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714–26.

Article  CAS  PubMed  Google Scholar 

Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP–dependent transporters. Nat Rev Cancer. 2002;2(1):48–58.

Article  CAS  PubMed  Google Scholar 

Vara JÁF, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193–204.

Article  CAS  Google Scholar 

Ghiaur G, Ferkowicz MJ, Milsom MD, Bailey J, Witte D, Cancelas JA, et al. Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells. Blood J Am Soc Hematol. 2008;111(7):3313–21.

CAS  Google Scholar 

Junttila MR, De Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501(7467):346–54.

Article  CAS  PubMed  Google Scholar 

Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6(1):479–507.

Article  CAS  PubMed  Google Scholar 

Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277–84.

Article  CAS  PubMed  Google Scholar 

Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 2016;25(Suppl. 2):41–59.

Article  PubMed  Google Scholar 

Kovalchuk O, Kovalchuk I. Cannabinoids as anticancer therapeutic agents. Cell Cycle. 2020;19(9):961–89.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fraguas-Sánchez AI, Torres-Suárez AI. Medical use of cannabinoids. Drugs. 2018;78(16):1665–703.

Article  PubMed  Google Scholar 

Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anticancer drug. Br J Clin Pharmacol. 2013;75(2):303–12.

Article  CAS  PubMed  Google Scholar 

Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int J Cancer. 2007;121(10):2172–80.

Article  CAS  PubMed  Google Scholar 

Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Anticancer Res. 2011;31(11):3799–807.

CAS  PubMed  PubMed Central  Google Scholar 

Kargl J, Haybaeck J, Stančić A, Andersen L, Marsche G, Heinemann A, et al. O-1602, an atypical cannabinoid, inhibits tumor growth in colitis-associated colon cancer through multiple mechanisms. J Mol Med. 2013;91:449–58.

Article  CAS  PubMed  Google Scholar 

Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine. 2014;21(5):631–9.

Article  CAS  PubMed  Google Scholar 

Martínez-Martínez E, Martín-Ruiz A, Martín P, Calvo V, Provencio M, García JM. CB2 cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3β signaling pathway. Oncotarget. 2016;7(42):68781.

Article  PubMed  PubMed Central  Google Scholar 

Hasenoehrl C, Feuersinger D, Sturm EM, Bärnthaler T, Heitzer E, Graf R, et al. G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1. Int J Cancer. 2018;142(1):121–32.

Article  CAS  PubMed  Google Scholar 

Honarmand M, Namazi F, Mohammadi A, Nazifi S. Can cannabidiol inhibit angiogenesis in colon cancer? Comp Clin Pathol. 2019;28:165–72.

Article  CAS  Google Scholar 

Jeong S, Kim BG, Kim DY, Kim BR, Kim JL, Park SH, et al. Cannabidiol overcomes oxaliplatin resistance by enhancing NOS3-and SOD2-induced autophagy in human colorectal cancer cells. Cancers. 2019;11(6):781.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim JL, Kim BR, Kim DY, Jeong YA, Jeong S, Na YJ, et al. Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. Cancers. 2019;11(5):642.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang X, Qin Y, Pan Z, Li M, Liu X, Chen X, et al. Cannabidiol induces cell cycle arrest and cell apoptosis in human gastric cancer SGC-7901 cells. Biomolecules. 2019;9(8):302.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jeong S, Jo MJ, Yun HK, Kim DY, Kim BR, Kim JL, et al. Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer. Cell Death Dis. 2019;10(11):846.

Article  PubMed  PubMed Central  Google Scholar 

Sainz-Cort A, Müller-Sánchez C, Espel E. Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum. BMC Res Notes. 2020;13(1):389.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cerretani D, Collodel G, Brizzi A, Fiaschi AI, Menchiari A, Moretti E, et al. Cytotoxic effects of cannabinoids on human HT-29 colorectal adenocarcinoma cells: different mechanisms of THC, CBD, and CB83. Int J Mol Sci. 2020;21(15):5533.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nkune NW, Kruger CA, Abrahamse H. Possible enhancement of photodynamic therapy (PDT) colorectal cancer treatment when combined with cannabidiol. Anti-Cancer Agents Med Chem (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2021;21(2):137–48.

Article  CAS  Google Scholar 

Ben-Ami Shor D, Hochman I, Gluck N, Shibolet O, Scapa E. The cytotoxic effect of isolated cannabinoid extracts on polypoid colorectal tissue. Int J Mol Sci. 2022;23(19):11366.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nkune NW, Kruger CA, Abrahamse H. Synthesis of a novel nanobioconjugate for targeted photodynamic therapy of colon cancer enhanced with cannabidiol. Oncotarget. 2022;13:156.

Article  PubMed  PubMed Central  Google Scholar 

Benedicto A, Arteta B, Duranti A, Alonso-Alconada D. The synthetic cannabinoid URB447 exerts antitumor and antimetastatic effect in melanoma and colon cancer. Pharmaceuticals. 2022;15(10):1166.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yüksel B, Hızlı Deniz AA, Şahin F, Sahin K, Türkel N. Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells. Front Pharmacol. 2023;14:1145666.

Article  PubMed 

Comments (0)

No login
gif