Cannabidiol and Cannabis Sativa as a potential treatment in vitro prostate cancer cells silenced with RBBp6 and PC3 xenograft

Abstract

Background Prostate cancer is the second most frequently occurring carcinoma in males worldwide and one of the leading causes of death in men around the world. Recent studies estimate that over 1.4 million males are diagnosed with prostate cancer on an annual basis, with approximately 375,000 succumbing to the disease annually. With current treatments continuing to show severe side effects, there is a need for new treatments. In this study we looked at the effect of cannabis sativa extract, cannabidiol and cisplatin on prostate cancer cells, PC3. Methods In addressing the above questions, we employed the MTT assay to measure the antiproliferative effect on PC3 cells following treatment with varying concentrations of Cannabis sativa extract, cisplatin and cannabidiol. xCELLigence was also used to confirm the IC50 activity in which cells were grown in a 16 well plate coated with gold and monitor cell attachment. Caspase 3/7 activity was also measured using 96 well-plate following treatment. Western-blot and qRT-PCR was also used to measure the gene expression of tumour suppressor genes, p53, Bax and Bcl2. Animal studies were employed to measure the growth of PC3-mouse derived cancer to evaluate the effect of compounds in vivo. Results From the treatment with varying concentrations of Cannabis sativa extract, cannabidiol and cisplatin, we have observed that the three compounds induced antiproliferation of PC3 cancer cell lines through the activation of caspase 3/7 activity. We also observed induction of apoptosis in these cells following silencing of retinoblastoma binding protein 6 (RBBP6), with upregulation of p53 and bax mRNA expression, and a reduction in Bcl2 gene expression. The growth of tumours in the mouse models were reduced following treatment with cisplatin and cannabidiol. Conclusion We demonstrated that cannabidiol is a viable therapy to treat prostate cancer cells, in combination with silencing of RBBP6. This suggests that cannabidiol rather Cannabis sativa extract may play an important role in reducing cancer progression.

Treatment of malignant diseases with phytocannabinoids: promising observations in animal models and patients

“…TRPV1 is expressed in all four prostate cancer cell lines, with the highest expression found in DU-145 cells, whereas TRPM8 receptor has been found in LNCaP cells [137,138]. In vitro, CBD can inhibit the expression of the AR in AR+ cell lines [139]; CBD is also a TRPM8 antagonist. In vivo, results are actually restricted to only two studies that are summarised below (Table 14).…”

Anti-Cancer and Anti-Proliferative Potential of Cannabidiol: A Cellular and Molecular Perspective

“…However, the popularised psychotic effects of cannabis and its widespread distribution as an illicit drug led to the marginalization and criminalization of this natural evergreen in the 20th century, ultimately impeding medicinal research on the previously documented medicinal properties of this plant [2,6]. Cannabinoids (CBNs) are a large group of naturally occurring compounds; this diverse group of approximately 120 cannabinoids is classified into three major categories: phytocannabinoids (found in Cannabis sativa), endocannabinoids (physiologically produced in humans), and synthetic cannabinoids that are structurally similar to both phyto-and endocannabinoids [1,7]. Two major CBNs, THC and CBD (Figure 1), have been identified as the main bioactive compounds playing critical roles in biological systems and have thus attracted the attention of clinical researchers, owing to their potential as therapeutic agents in the medical and health industries for applications in anti-cancer therapy [7].…”

“…Cannabinoids (CBNs) are a large group of naturally occurring compounds; this diverse group of approximately 120 cannabinoids is classified into three major categories: phytocannabinoids (found in Cannabis sativa ), endocannabinoids (physiologically produced in humans), and synthetic cannabinoids that are structurally similar to both phyto- and endocannabinoids [ 1 , 7 ]. Two major CBNs, THC and CBD ( Figure 1 ), have been identified as the main bioactive compounds playing critical roles in biological systems and have thus attracted the attention of clinical researchers, owing to their potential as therapeutic agents in the medical and health industries for applications in anti-cancer therapy [ 7 ]. For instance, cannabinoids are effective antiemetics against nausea and vomiting in patients with cancer receiving chemotherapy [ 8 , 9 ].…”

Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells

“…Sharma et al reported that a whole plant extract containing CBD and other cannabinoids inhibited LNCaP cell viability, accompanied by reduced expression of AR and prostate-specific antigen (PSA) . Additionally, Motadi et al reported that CBD reduced cell viability and increased caspase activity in hormone-resistant PC-3 cells, accompanied by increased expression of p53 and Bax . More recently, Mahmoud et al investigated the role of metabolic signaling in the induction of cell death by CBD.…”

“… 10 Additionally, Motadi et al reported that CBD reduced cell viability and increased caspase activity in hormone-resistant PC-3 cells, accompanied by increased expression of p53 and Bax. 11 More recently, Mahmoud et al investigated the role of metabolic signaling in the induction of cell death by CBD. They reported that CBD reduced cell viability and increased caspase activity in both hormone-naïve and hormone-resistant transgenic adenocarcinoma mouse prostate (TRAMP) cell line models, effects that were associated with increased glycolytic capacity, inhibition of oxidative phosphorylation and ATP production, and altered expressed of genes and proteins involved in regulating mitochondrial activity.…”