RESUMEN
Forsythiae Fructus, the fruits of Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, we investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-[Formula: see text] and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE.
Asunto(s)
Antiinflamatorios/administración & dosificación , Antineoplásicos/administración & dosificación , Antioxidantes/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Forsythia/química , Hemo-Oxigenasa 1/metabolismo , Melanoma Experimental/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Hemo-Oxigenasa 1/genética , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/fisiopatología , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
Evodiamine (EVO) is a plant-derived indolequinazoline alkaloid with potential anticancer activity. However, low bioavailability caused by its poor water solubility limits it anticancer efficacy in clinic. To enhance the solubility and improve the bioavailability of EVO, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with EVO (EVO-PLGA NPs) for treating breast cancer was prepared in this study. The physicochemical characterization and in vitro antitumor evaluation of EVO-PLGA NPs were determined. EVO-PLGA NPs could persistently control the release of EVO for 180 h. 3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assessment and colony formation assay showed that EVO-PLGA NPs could enhance the toxicity and the proliferation inhibition effect of EVO on MCF-7 breast cancer cells. EVO-PLGA NPs did not strengthen G2/M arrest effect of EVO-treated cells after 24h incubation. Meanwhile, EVO-PLGA NPs could increase the expression of cyclin B1 and decrease the expression of ß-actin. Taken together, these results suggested that -PLGA NPs is promising for improving anticancer efficacy of EVO in breast cancer therapy.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Quinazolinas/química , Quinazolinas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Femenino , Humanos , Células MCF-7 , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 µM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 µM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.