Anti-Cancer Activity of Dendrobium chrysotoxum in human prostate cancer cells

Dendrobium is one of the most valuable herbs in traditional Chinese medicine (TCM). It’s bibenzyl compounds demonstrate promising anti-cancer properties. Prostate cancer is the second most common cancer in men with estimated 1.1 million new cases and 0.8 million deaths per year in 2012. While Dendrobium’ anti-cancer activities has been explored in several cancer cell lines, the investigation of their bioactivity on prostate cancer is generally limited. Therefore, this thesis examines bioactivity and molecular mechanisms of selected Dendrobium species and their isolated chemical constituents in the three prostate cancer cell lines, LNCaP, an androgen dependent prostate cancer cell line, PC3 and DU-145, two non-dependent androgen cell lines. The study began with the screening of ten Dendrobium species commonly used in TCM practice, Dendrobium anosnum, D. aphyllum, D. devonianum, D. officinale, D. nobile, D. loddigesi, D. parisii, D. fimbriatum, D. aduncum, and D. chrysotoxum. Bioassay-guided fractionation techniques were applied to isolate and characterise the active compounds of the Dendrobium species that possess anti-cancer activity against the three prostate cancer cells. The crude extract of all ten Dendrobium species showed promising inhibitory effects on the three selected prostate cancer cell lines at a concentration of 20µg/mL. D. chrysotoxum exhibited the strongest anti-cancer activity which was then subjected to further investigation. Isolation, purification and elucidation procedures revealed that erianin is the predominant bibenzyl compound in D. chrysotoxum and is responsible for its anti-cancer activity. Our initial findings confirmed that erianin, is highly abundant in D. chrysotoxum, whereas other studies showed it is present in a much lower amounts in other Dendrobium species. Dendrobium species vary widely in their chemical constituents, and several factors including geographic, climatic and season of harvesting influence their quantity and quality. Hence, the almost exclusive presence of erianin in D. chrysotoxum could be applied for standardization and quality control of the anti-cancer properties of this Dendrobium species. Erianin exhibited anti-cancer activity in prostate cancer cells with an IC50 value below 50nM signifying its potency as a promising anti-cancer agent. At 24 hours of treatment, the IC50 of erianin for LNCaP cells is about twice the IC50 of PC3, while at a longer treatment times, the IC50 values of the two prostate cancer cells lines were similar, of 32.96nM for LNCaP and 36.06nM for PC3, at 72 hours of treatment. While erianin exhibits strong inhibition of cancer cell viability, erianin has no effect on the migration of either LNCaP and PC3 cells. The anti-cancer mechanism of erianin was further explored on LNCaP and PC3 cells representing the two different types in androgen dependence of prostate cancer. Erianin showed a different anti-cancer mechanism of action between the two prostate cancer cell lines. In androgen sensitive LNCaP, erianin induced apoptosis and autophagy. However, in androgen insensitive PC3 cells it induced autophagy and G2/M phase arrest. This thesis then compares erianin’s anti-cancer mechanism in prostate cancer cells with the mechanisms that have been identified in other previously studied cancer cell lines and discusses the underlying mechanism of erianin anticancer bioactivity. The anti-cancer activity of erianin on prostate cancer cell lines through induced apoptosis, autophagy and cell cycle arrest aligns with its bioactivity in other cell lines. Our study lays the essential findings of the potency of erianin against both androgen dependent and androgen independent prostate cancer cells, further elucidation of the mechanism and validation with in vivo experiments are required