RESUMO
BACKGROUND: Tanshinone IIA (Tan-IIA) is one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae Radix. We explored the mechanisms of cell death induced by Tan-IIA treatment in prostate cancer cells in vitro and in vivo. METHODS: Cells were treated with Tan-IIA and growth inhibition was assessed. Cell cycle profiles after Tan-IIA treatment were determined by flow cytometry. Expression levels of cell cycle regulatory proteins and apoptosis-related proteins were determined after Tan-IIA treatment. Expression levels of endoplasmic reticulum (ER) stress-regulated genes were determined to investigate their role in Tan-IIA-induced cell death. GADD153 expression was knocked down by small interfering RNA (siRNA) transfection. Rate of cell death and proliferation was obtained by 3-(4,5-dimethyl thizol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Antitumor activity of Tan-IIA was performed in LNCaP xenograft model. RESULTS: Our results showed that Tan-IIA caused prostate cancer cell death in a dose-dependent manner, and cell cycle arrest at G0/G1 phase was noted, in LNCaP cells. The G0/G1 phase arrest correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. Tan-IIA also induced ER stress in prostate cancer cells: activation and nuclear translocation of GADD153/CCAAT/enhancer-binding protein-homologous protein (CHOP) were identified, and increased expression of the downstream molecules GRP78/BiP, inositol-requiring protein-1α and GADD153/CHOP were evidenced. Blockage of GADD153/CHOP expression by siRNA reduced Tan-IIA-induced cell death in LNCaP cells. Tan-IIA also suppressed LNCaP xenograft tumor growth, causing 86.4% reduction in tumor volume after 13 days of treatment. CONCLUSIONS: Our findings suggest that Tan-IIA causes G0/G1 cell cycle arrest in LNCaP cells and its cytotoxicity is mediated at least partly by ER stress induction. These data provide evidence supporting Tan-IIA as a potential anticancer agent by inducing ER stress in prostate cancer.
Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias da Próstata/genética , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Three new saponins named Julibroside J1, J2 and J3 were isolated from the stem bark of Albizzia julibrissin Durazz (Albizziae Cortex). Based on chemical and spectral methods, e.g. 1H- and 13C-NMR, DEPT, COSY CH-COSY, TOCSY, HMQC-COSY, HMQC-TOCSY, NOESY, HMBC, their structures have been identified as; Julibroside J1 (one triterpene, nine sugars, two monoterpenes I); Julibroside J2(one triterpene, eight sugars two monoterpenes II); Julibroside J3(one triterpene, nine sugars two monoterpenes III).
Assuntos
Antineoplásicos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Fabaceae/química , Monoterpenos , Plantas Medicinais , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Antineoplásicos/química , Estrutura Molecular , Caules de Planta/química , Saponinas/química , Triterpenos/químicaRESUMO
A new sapogenin named Julibrogenin A was isolated from the stem bark of Albizzia julibrissin Durazz (Albizziae Cortex). Based on chemical and spectral studies, their structure has been identified as 21-O-(2-hydroxymethyl-6-methyl-6-methoxyl-2,7-octadienoyl)-acacic acid. In addition, machaerinic acid lactone, machaerinic acid methylester, acacigenin B and julibrotriterpenoidal lactone A were also isolated from this plant and characterised.
Assuntos
Medicamentos de Ervas Chinesas/química , Fabaceae/química , Plantas Medicinais , Triterpenos/químicaRESUMO
In this paper, the regularity on spontaneous discharges of the single unit in amygdaloid nucleus (AMYG) in rabbits were analyzed and whether the signal of Electro-acupuncture (EA) at Neiguan (P 6) can reach the AMYG was further observed with the technique of glass microelectrode. It was found that the signals of EA at Neiguan can reach AMYG and activate or inhibit the electrical activity of some neurons, manifesting two response patterns: frequency-increasing and frequency-decreasing. Additionally, the same neuron had a different response to the signals of EA at Neiguan and Zusanli (St 36), suggesting that a relative specificity of acupoints is present.