Research Of Anti-throat Cancer Effects And Mechanisms Of Two Medicinal Plants G. Bracteata And S. Moellendorfii

Throat cancer is one of the classical head and neck malignant tumors with a relatively high mortality rate.Although breakthrough headway has been made in the diagnosis and cure of throat cancer,its prognosis has not been significantly improved.However,these commonly used clinical treatment methods are not appropriate for all patients,accompanied by shortcomings such as strong side effects and irreparable trauma to patients,affecting their quality of life.Hence,it is urgent to explore anti-throat cancer drugs with strong specificity,stable curative effect,less adverse reactions and small side effects.Medicinal plants are the vital source to discover natural products with antineoplastic activity.Their characteristics of high efficiency and low toxicity have aroused great concern in the territory of cancer treatment,and they have very long-term clinical medication experience and clear clinical efficacy.As the main source of most novel tumor chemotherapy drugs,medicinal plants have high development and utilization value.Therefore,it has great potential to develop new anti laryngopharyngeal cancer drugs from medicinal plants.Our group used the MTT technique to screen the cytotoxicity of Chinese herbal medicine and ethnic medicine extract library and found that extracts of Garcinia bracteata C.Y.Wu ex Y.H.Li and Selaginella moellendorfii Hieron.have showed promising inhibitory effect on throat cancer cells.This paper is designed to research the anti-throat cancer activity of the chemical active components isolated and identified from these two medicinal plants and determine their molecular mechanism.The main results are as follows.1.Research on anti-throat cancer effects and mechanisms of a composition of two prenylxanthones from the fruits of G.bracteataPrenylxanthone,as the major bioactive substance isolated from the genus Garcinia,possesses significant anti-cancer effects.But its antineoplastic activity and molecular mechanism of action in throat cancer have not been reported yet.In this study,a composition of two prenylxanthones(CPX)from the fruits of G.bracteata was obtained to clarify its chemical composition,anti-throat cancer ability and underlying mechanism in vitro and in vivo.The data revealed that CPX,composed of bractatin and neobractatin,dose-dependently suppressed human laryngeal cancer cell line Hep-2 and pharyngeal cancer cell line Fa Du proliferation and promoted apoptosis,and meanwhile retarded xenografts growth in nude mice with no obvious toxicity.Western blot analysis demonstrated that CPX exerted anti-throat cancer effect by inducing apoptosis through endoplasmic reticulum stress,mitochondrial apoptotic and Akt pathways.All results suggested that CPX could be considered as a potential chemotherapeutic drug for throat cancer.2.Research on anti-laryngeal carcinoma effects and mechanisms of a biflavonoid-rich extract from S.moellendorfiiSelaginella moellendorfii Hieron.,a perennial evergreen plant,has been used in the treatment of acute infectious hepatitis,thoracic and hypochondriac lumbar contusions,systemic edema,and thrombocytopenia.However,the role of a biflavonoid-rich extract from S.moellendorfii in anti-larynx cancer has rarely been reported.In this study,the in vitro and in vivo anti-laryngeal cancer activity and potential mechanisms of SM-BFRE were investigated.An off-line semipreparative liquid chromatography-nuclear magnetic resonance protocol was implemented to determine six biflavonoids from SM-BFRE.In vitro,MTT analysis pointed out that SM-BFRE restrained the growth of laryngeal carcinoma cells Hep-2 and TU212.Cell scratch assay indicated that SM-BFRE suppressed the migration of laryngeal cancer cells.Hoechst 33258 and Annexin V-FITC/PI double staining assays were performed and verified that SM-BFRE induced apoptosis in laryngeal carcinoma cells.The Hep-2 bearing nude mice model confirmed that SM-BFRE also exhibited obvious anticancer effect in vivo.In addition,western blot analysis demonstrated that SM-BFRE exerted its anti-laryngeal cancer effect by activating the mitochondrial apoptotic pathway and inhibiting STAT3 and Akt/NF-κB signaling pathways.All results suggested that SM-BFRE could be regarded as a latent chemotherapeutic drug for laryngeal carcinoma.These results indicated that extracts of G.bracteata and S.moellendorfii showed significant anti-throat cancer potency.MTT method provided a simple and convenient way to explore new drugs for the treatment of throat cancer;Western blot experiment was carried out to determine the signal transduction pathways against throat cancer quickly;simultaneously,the beneficial combination of cell manipulation in vitro and animal experiment in vivo has mutually verified their anti-throat cancer activity.