Targeting Nrf2 Signaling Pathway in Cancer Prevention and Treatment: The Role of Cannabis Compounds

Abstract

The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2. Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells—influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support. In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy.

New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy

“…Not only ∆9-THC, but also CBD has been evaluated in clinical trials in the context of GBM treatment. The molecular mechanisms responsible for the anti-tumor effect exerted by CBD include, among others, targeting glioma stem cells and cancer-related signaling pathways [107,108], influencing the tumor microenvironment (TME) [109], and producing reactive oxygen species (ROS) in tumor cells [110]. Overall, numerous in vitro and in vivo studies showing beneficial effects of CBD against GBM cells (just to mention a few most recent studies [107,[109][110][111][112]) paved the way for clinical trials evaluating the impact of this cannabinoid on humans.…”

The Effect of Phytocannabinoids and Endocannabinoids on Nrf2 Activity in the Central Nervous System and Periphery

“…This suggests a possible role played by this endocannabinoid in the Nrf2 pathway activation, as well as its potential involvement in chemotherapy resistance. Indeed, the role of cannabinoids on Nrf2-related factors has been recently reviewed in the context of cancer prevention and treatment [ 86 ], with an amount of evidence reporting the beneficial and protective role provided by the modulation of AEA/HO-1 signaling as a coadjutant pharmacological approach to reduce radio resistance and chemoresistance [ 85 ].…”

Cadmium-induced Carcinogenesis in Respiratory Organs and the Prostate: Insights from Three Perspectives on Toxicogenomic Approach

“…They could be considered KEs. The change in HMOX1 expression affects apoptosis [ 57 ]. Oxidative stress caused by Cd can lead to DNA damage [ 58 ], and apoptosis resulting from DNA damage could be influenced by Cd exposure.…”