Prostate cancer (PC) is one of the major causes of death among men worldwide. Currently, prostate cancer accounts for 14% of all male malignancies, PC remains the most diagnosed cancer in men in over one-half of the world's countries and is second most frequently occurring cancer in men worldwide. Prostate cancer is rated fifth leading cause of cancer-related deaths in men worldwide in the year 2020. Even though the exact origin of prostate cancer is unknown, several factors, including age, family history, lifestyle factors, and testosterone levels, are linked to a higher chance of acquiring the disease1, 2, 3.
Cannabinoids are naturally compounds found in the Cannabis sativa plant and are classified into three categories based on their origin: plant-derived cannabinoids such as ∆9- tetrahydrocannabinol (∆9-THC), endocannabinoids and mock molecules that mimic the structure of either plant or mammalian cannabinoids. More than 50 phytocannabinoid entities are found in cannabis plant extracts, with cannabidiol (CBD) being themain clinical interest being and tetrahydrocannabinol (THC) 4, 5, 6. In recent years, cannabinoids have gained more interest in treating side effects associated with chemotherapy, such as nausea. There is also growing interest in the anti-cancer potential of Cannabis sativa secondary metabolites. However, there is little data to support their use or effectiveness in cancer treatment. Research has demonstrated that cannabinoids possess some anti-cancer properties since the identification of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)7, 8. CBD accounts for 40% of Cannabis sativa plant extracts, and this compound's concentration depends on the geographical impact from where the plant originated11. CBD has been found to elicit anti-proliferative and apoptotic effects in breast cancer cell lines, MDA-MB 321 and MDA-MB 436 9, 10. Several studies have acknowledged cannabidiol possesses anti-cancer properties against several cancers, but none has reported their effect with co-treatment with other cancer therapies12, 13. Despite the lack of a described and understood molecular mechanism of action, CBD is still the most effective cannabinoid for use in developing anti-cancer drugs14.
Researchers have resorted to animal tumor models as they are a reliable predictor in preclinical cancer research, given that they can produce reliable tumor growth. Although many studies have examined the impact of cannabis on prostate cancer in cell culture experiments, very few papers have established if these effects occur in in vivo animal models. Few publications have suggested whether these effects could be repeated in in vivo animal models, regardless of the fact that several studies have explored the efficacy of cannabinoids on prostate cancer in cell culture studies15. Numerous studies have been done on CBD concerning various cancers, including prostate and lung cancer [16]. Some of these studies discovered that the extracts of cannabis enhanced with CBD effectively reduced the growth of tumors in androgen receptor-positive LNCaP xenografts but amplified tumor growth in androgen receptor-negative DU-145 xenografts. Correspondingly, to determine the effects of CBD in vivo, the xenograft mouse models 17. The migration/invasion and viability of the HNSCC cells have been drastically reduced in a dose- and time-dependent manner18, 19. In other studies unrelated to cancer, CBD had no effect on heart rate under normal conditions, but in animal stress models, CBD reduces heart rate and blood pressure20, 21, 22. Results from studies conducted on humans and animals interpret/illustrate that CBD possesses extremely different effects compared to THC23, 24. Although these studies show cannabinoids have the potential to target prostate cancer, there is still the need to implement more research to conclusively establish the efficacy of cannabinoids in vivo and the importance of co-treatment with either gene therapy or chemotherapy.
In a number of malignancies, including oesophageal cancer28, breast cancer29, lung cancer30, and cervical cancer31, retinoblastoma-binding protein 6 (RBBP6), which regulates cell proliferation, cell cycle, and cell apoptosis, is greatly up-regulated and is associated with poor clinical prognosis. Cell cycle arrest, a characteristic of carcinogenesis that is caused by RBBP6 overexpression, is significantly linked to the growth of cervical and oesophageal cancer tumors6, 8.This, therefore, suggests that RBBP6 may serve a critical role in the malignant phenotype of human cancer 6, 9, 10. In addition to this, the results indicated that RBBP6 may promote tumorigenesis by increasing cancer cell proliferation.
In this study, we investigated the anti-cancer properties of Cannabis sativa extract, CBD and cisplatin on prostate cancer cells, PC3, in combination with siRBBP6 gene therapy.