Tag: colorectal cancer

Abstract

Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.

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Abstract

Colorectal cancer (CRC) is the leading cause of cancer deaths worldwide, wherein distant metastasis is the main reason for death. The non-psychoactive phytocannabinoid cannabidiol (CBD) effectively induces the apoptosis of CRC cells. We investigated the role of CBD in the migration and metastasis of CRC cells. CBD significantly inhibited proliferation, migration, and invasion of colon cancer cells in a dose- or time-dependent manner. CBD could also inhibit epithelial–mesenchymal transition (EMT) by upregulating epithelial markers such as E-cadherin and downregulating mesenchymal markers such as N-cadherin, Snail, Vimentin, and HIF-1α. CBD could suppress the activation of the Wnt/β-catenin signaling pathway, inhibit the expression of β-catenin target genes such as APC and CK1, and increase the expression of Axin1. Compared to the control group, the volume and weight of orthotopic xenograft tumors significantly decreased after the CBD treatment. The results demonstrated that CBD inhibits invasion and metastasis in CRC cells. This was the first study elucidating the underlying molecular mechanism of CBD in inhibiting EMT and metastasis via the Wnt/β-catenin signaling pathway in CRC cells. The molecular mechanism by which CBD inhibits EMT and metastasis of CRC cells was shown to be through the Wnt/β-catenin signaling pathway for the first time.

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Abstract

Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood. In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4. We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.

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Abstract

Recently, cannabinoids, such as cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), have been the subject of intensive research and heavy scrutiny. Cannabinoids encompass a wide array of organic molecules, including those that are physiologically produced in humans, synthesized in laboratories, and extracted primarily from the Cannabis sativa plant. These organic molecules share similarities in their chemical structures as well as in their protein binding profiles. However, pronounced differences do exist in their mechanisms of action and clinical applications, which will be briefly compared and contrasted in this review. The mechanism of action of CBD and its potential applications in cancer therapy will be the major focus of this review article.

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Abstract

Colon cancer is the third most common human malignancy and a main cause of death worldwide. The current study was carried out to investigate the effects of cannabidiol, a cannabinoid, on angiogenesis and cell death in mice with experimental colon cancer induced by injection of CT26 cell line. Fifty male BALB/c mice were assigned randomly to five study groups, including: (1) negative control, (2) cancer control, (3) cancer vehicle control, (3) cancer treatment (1 mg/kg cannabidiol), and (5) cancer treatment (5 mg/kg cannabidiol). Treatment responses were evaluated based on histopathological examination, the expression of vascular endothelial growth factor (VEGF) gene, measurement of interleukins (ILs 6 and 8), oxidative stress parameters (glutathione peroxidase, glutathione reductase, superoxide dismutase serum activities, total antioxidant capacity, and malondialdehyde levels). In the present study, CBD reduced VEGF gene expression, decreased serum levels of IL6, IL8, and malondialdehyde, and increased antioxidant enzyme activity in mice with colon cancer. Moreover, cannabidiol induced apoptosis and reduced cellular pleomorphism. Cannabidiol can be potentially considered as an anti-colon cancer medicine as it exerts an inhibitory effect on angiogenesis, tumor growth, and metastasis through reducing VEGF gene expression, decreasing cytokines, and increasing antioxidant enzyme activities.

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