α-Pinene Inhibits Human Prostate Cancer Growth in a Mouse Xenograft Model

Abstract

Background: α-Pinene is one of the most widely found terpenoids in nature. Substantial evidence shows that α-pinene has cancer prevention properties. In this study, the PC-3 cell line was used to establish subcutaneous xenograft tumors in nude mice. Methods: Cytotoxicity was measured with the MTT assay, and apoptosis and cell cycle analyses were conducted using flow cytometry in vitro. The PC-3 cell line was used to establish subcutaneous xenograft tumors in nude mice. Results: We found that treatment with α-pinene significantly inhibited human prostate cancer cell growth and induced apoptosis and cell cycle arrest in the cell line-based model. Furthermore, tumor progression was inhibited more in mice treated with α-pinene than in control mice. We detected less Ki67 and proliferation cell nuclear antigen in paraffin sections from xenograft tumor specimens taken from α-pinene-treated mice than in those from the control group. Meanwhile, α-pinene treatment induced apoptosis in xenograft tumors as determined by the TUNEL assay. Conclusions: These data strongly suggest that α-pinene inhibits prostate cancer growth in a xenograft model and may be an effective therapeutic agent for prostate cancer treatment.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…The inhibition of cell cycle transition between the G2 and M phase shown by Chen et al was also seen in PA-1 and HepG2 cells [187,188]. α-pinene inhibited PC-3 human prostate cancer cell growth, induced apoptosis, and reduced tumor progression in mice with xenograft tumors [189]. In melanoma cells, α-pinene increased ROS production and early apoptotic features such as DNA fragmentation and phosphatidylserine on the cell surface, as well as disruption of the mitochondrial membrane potential.…”

“…Reduced cell viability [187][188][189][190]. Induced apoptosis [187][188][189]191,192]. Increased ROS production [188,191].…”

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

“…In the plant, these compounds (i.e., more than 120 terpenes) synthesized alongside phytocannabinoids are important volatile constituents that are responsible for the plant's characteristic smell and also serve for different organic functions, such as insect repellent, repellent to herbivore attack, and attractive to pollinators [71]. Booth and Bohlmann described the terpenes-and cannabinoid-rich resin as the most valuable cannabis products, with different psychoactive and medicinal properties [83]. Studies regarding terpenoid compounds (i.e., D-limonene, β-myrcene, α-pinene, α-terpineol, β-pinene, β-caryophyllene, and others) have been growing in the last decades due to their large number and extensive employability [71,84].…”

“…Alpha-pinene is considered a natural compound present not only in Cannabis sativa but also in essential oils of many aromatic plants, such as Lavender angustifolia, Rosmarinus officinalis, and coniferous trees [149]. Alpha-pinene is a bicyclo[3.1.1]hept-2-ene that contains a reactive 4-membered ring structure and exhibits antioxidant, antimicrobial, anti-tumor, hypnotic, and anxiolytic activities [83,120,[150][151][152]. There are different biological properties described to α-pinene, as well as essential oils containing this compound have been used to treat several diseases [153], although no affinity towards CBRs have been described [154].…”

Programmable gene regulation for metabolic engineering using decoy transcription factor binding sites

“…As a showcase of sponge tolerance libraries, we sought to enhance tolerance to α-pinene, an important monoterpene that can be produced in E. coli (34). Pinene is of interest to metabolic engineers as it has many potential uses, such as an alternative jet fuel, flavoring and fragrance additive, and a therapeutic agent (34)(35)(36). Production of pinene is toxic to E. coli and growth is inhibited in 0.5% pinene (v/v).…”