RESUMO
Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor ß (TGF-ß) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-ß treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-ß. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.
RESUMO
Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays critical roles in the development and progression of hepatocellular carcinoma (HCC). Artemisia capillaris (AC) has been widely used to treat various liver diseases including HCC as a herbal medicine. The effects of AC on IL-6/STAT3 signaling axis in HCC cells and subsequent anticancer activity of AC against HCC were analyzed using HCC cell lines and HBV W4P-LHB-expressing NIH3T3 cell line, which has been shown to gain tumorigenicity by activating IL-6/STAT3 signaling in our previous study. AC extract significantly suppressed the growth and colony formation of HCC cells. In addition, it inhibited the activation of STAT3 by IL-6 and subsequent synthesis of downstream molecules in HCC and W4P-NIH3T3 cells. Consequently, migration of cells was significantly suppressed by the AC extract. Collectively, the findings suggest that AC extract is capable of conferring various antitumor effects against HCC through the modulation of the IL-6/STAT3 pathway. The results provide a basis for the therapeutic use of AC in the treatment of HCC. Identification of the compound responsible for the effect may lead to the development of a novel anticancer agent against HCC.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Células NIH 3T3 , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Shikonin (SK), a natural naphthoquinone isolated from the Chinese medicinal herb, has been known to suppress the proliferation of several cancer cells. However, its role in the epithelial mesenchymal transition (EMT) has yet to be demonstrated. The aim of the present study was to examine the effects of SK on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. SK markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin in MDA-MB231 cells, and increased the expression of E-cadherin in MCF-7 cells. SK also inhibited cell migration and invasion in vitro. The effects of SK on the LPS-induced EMT were mediated by the inactivation of the NF-κB-Snail signaling pathway. The results provided new evidence that SK suppresses breast cancer cell invasion and migration by inhibiting the EMT. Therefore, SK is a potentially effective anticancer agent for breast tumors, by inhibiting metastasis.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Naftoquinonas/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Células MCF-7 , Microscopia de Fluorescência , Fatores de Transcrição da Família Snail , Fator de Transcrição RelA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Prunella vulgaris (PV) inhibits the proliferation of various cancer cells; however, its possible role in EMT has not been demonstrated. In the present study, we explored the effect of PV aqueous extract (PVAE), a typical medicine for decoction, on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotype changes in cancer cell lines that enhanced cell migration and invasion. PVAE markedly inhibited these effects and produced accompanying changes in the expression of EMT markers, including decreased expression of N-cadherin and vimentin, and increased expression of ß-catenin. We found that PVAE effects on LPS-induced EMT were mediated by inhibition of the NF-κB/Snail signaling pathway. Our findings provide new evidence that PVAE suppresses cancer invasion and migration by inhibiting EMT. Therefore, we suggest that PVAE is an effective dietary chemopreventive agent with antimetastatic activity against malignant tumors.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Transição Epitelial-Mesenquimal/imunologia , Lipopolissacarídeos/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/metabolismo , Invasividade Neoplásica , Extratos Vegetais/isolamento & purificação , Prunella/química , Fatores de Transcrição da Família Snail , Solventes/química , Fatores de Transcrição/metabolismo , Água/químicaRESUMO
Shikonin, a natural naphthoquinone isolated from the Chinese traditional medicine Zi Cao (purple gromwell), is known to suppress the growth of several cancer cell types. In this study, we evaluated the pro-apoptotic effects of shikonin on MCF-7 and HeLa cells, and investigated the underlying mechanism. Shikonin-induced apoptosis was associated with activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, up-regulation of p73, and down-regulation of BCL-2. Shikonin also induced up-regulation of the tumor suppressor gene, p16(INK4A). Increasing transcriptional activity of p16(INK4A) by shikonin treatment, we observed in luciferase promoter assay, reflects reduced promoter binding by down-regulation of ICBP90 (inverted CCAAT box binding protein, 90 kDa), which are involved in down-regulation of its partner, DNMT1 (DNA methyltransferase 1). On the basis of these results, we conclude that shikonin causes apoptosis via a p73-related, caspase-3-dependent pathway.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas Estimuladoras de Ligação a CCAAT/antagonistas & inibidores , Proteínas de Ligação a DNA/agonistas , Regulação Neoplásica da Expressão Gênica , Naftoquinonas/farmacologia , Proteínas Nucleares/agonistas , Proteínas Supressoras de Tumor/agonistas , Apoptose/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/agonistas , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Genes Reporter , Células HeLa , Humanos , Luciferases/genética , Luciferases/metabolismo , Células MCF-7 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína Tumoral p73 , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína LigasesRESUMO
The epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Psoralea corylifolia L. (PC) inhibits the proliferation of various cancer cells. However, its possible role in EMT has not been identified. In the present study, we examined the effects of an aqueous extract of Psoralea corylifolia L. (PCAE), a typical medicinal decoction, on the EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. However, PCAE markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin and vimentin, and increased the expression of ß-catenin. PCAE also inhibited cell migration and invasion in vitro. The effects of PCAE on the LPS-induced EMT were mediated by the inactivation of the NF-κB-SNAIL signaling pathway. The results provide new evidence that PCAE suppresses cancer cell invasion and migration by inhibiting EMT. Therefore, PCAE is a potentially effective dietary chemopreventive agent for malignant tumors since it inhibits metastasis.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Extratos Vegetais/farmacologia , Psoralea/química , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Humanos , NF-kappa B/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismoRESUMO
Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy.