RESUMEN
Ovarian cancer is a common and lethal cancer affecting women globally. Berbamine is a natural compound from the plant Berberis amurensis, which is used in Chinese traditional medicine. Recent studies have shown the anti-tumor effects of berbamine in several types of cancers but not in ovarian cancer. In the present study, we investigated the potential anti-tumor effects of berbamine in ovarian cancer and explored the underlying molecular mechanisms. Berbamine suppressed the cell viability of ovarian cancer cells in a concentration-dependent manner as revealed by methyl thiazolyl tetrazolium assay. Berbamine also suppressed the cell growth and invasion of ovarian cancer cells as measured by colony formation and cell invasion assays, respectively. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase in ovarian cancer cells. Western blot analysis showed that berbamine increased the protein levels of cleaved caspase-3, cleaved caspase-9, Bax, and decreased the protein level of Bcl-2 in ovarian cancer cells. Quantitative real-time PCR and western blot analysis demonstrated that berbamine treatment inhibited the Wnt/ß-catenin signaling in ovarian cancer cells. The inhibitory effects of berbamine on cell viability and invasion of ovarian cancer cells can be partially reversed by lithium chloride (LiCl) treatment. Growth of tumors developed from SKOV3 cells was significantly suppressed in berbamine-treated group, and berbamine treatment enhanced caspase-3 and -9 cleavage and reduced ß-catenin protein level in tumor tissues. In summary, berbamine exerts its anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the inhibition of Wnt/ß-catenin signaling.
Asunto(s)
Apoptosis/efectos de los fármacos , Bencilisoquinolinas/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Ováricas/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Bencilisoquinolinas/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/genéticaRESUMEN
Oxymatrine (OMT) has exhibited an anti-cancer role in human cancers, including cervical cancer (CC). The dysregulated circular RNAs (circRNAs) are key regulators in cancer biology, and circ_0008460 was upregulated in CC. This study was performed to investigate the circRNA-based molecular mechanism for OMT in CC. RNA detection for circ_0008460, microRNA-197-3p (miR-197-3p), or ribonucleotide reductase subunit M2 (RRM2) was completed using reverse transcription-quantitative polymerase chain reaction assay. Cell behaviors were assessed by Cell Counting Kit-8 assay for cell viability, colony formation assay or Edu assay for cell proliferation, flow cytometry for cell apoptosis, and wound healing assay/transwell assay for migration/invasion. Protein expression examination was conducted using western blot. Dual-luciferase reporter assay and RNA pull-down assay were applied to confirm target binding. Tumor xenograft assay was performed for OMT research in vivo. OMT induced circ_0008460 downregulation in CC cells. OMT-induced inhibitory effects on cell growth, migration, and invasion but promoting effect on cell apoptosis were attenuated by circ_0008460. Circ_0008460 directly interacted with miR-197-3p, and OMT inhibited malignant behaviors of CC cells via mediating circ_0008460/miR-197-3p axis. RRM2 acted as a target for miR-197-3p and circ_0008460 affected the RRM2 level through absorbing miR-197-3p. OMT upregulated miR-197-3p to inhibit RRM2 expression to impede CC cell development. CC tumorigenesis was suppressed by OMT via targeting circ_0008460/miR-197-3p/RRM2 axis in vivo. These results suggested that OMT restrained CC cell progression in vitro and tumor growth in vivo by downregulating circ_0008460 to mediate miR-197-3p/RRM2 axis.
Asunto(s)
MicroARNs , Neoplasias del Cuello Uterino , Alcaloides , Proliferación Celular/genética , Femenino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Quinolizinas , ARN Circular/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
Berbamine has been shown to exhibit anti-cancer activities in various types of cancers. The effects of berbamine on colorectal colon cancer (CRC) have not been examined, and the present study aimed to investigate the anti-cancer effects of berbamine in CRC and explore its underlying molecular mechanisms. The effect of berbamine on the CRC cells was determined by MTT assay. Flow cytometry was performed to examine the effect of berbamine on cell apoptosis and cell cycle as well as mitochondrial membrane potential in CRC cell lines. The specific apoptosis-related factors were evaluated by western blot assay. In vivo anti-cancer effect of berbamine was assessed in SW480 xenografts. Berbamine suppressed the cell viability of CRC cells in concentration-dependent and time-dependent manners. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase. Berbamine treatment also decreased the mitochondrial membrane potential in CRC cells. Western blot assay showed that berbamine increased the protein levels of p53, caspase-3, caspase-9, Bax and poly ADP ribose polymerase, and decreased the protein levels of Bcl-2 in CRC cells. Berbamine failed to increase the cell apoptotic rate in p53 mutant CRC cell lines. Tumor growth by grafted SW480 cells were significantly suppressed in berbamine group. Expression of p53, caspase-3 and -9 in tumor tissues was significantly up-regulated by berbamine. Berbamine exerts anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the activation of p53-dependent apoptosis signaling pathway.
RESUMEN
Completion of a survey of dermatoglyphic variables for all ethnic groups in an ethnically diverse country like China is a huge research project, and an achievement that anthropological and dermatoglyphic scholars in the country could once only dream of. However, through the endeavors of scientists in China over the last 30 years, the dream has become reality. This paper reports the results of a comprehensive analysis of dermatoglyphics from all ethnic groups in China. Using cluster analysis and principal component analysis of dermatoglyphics, it has been found that Chinese populations can be generally divided into a southern group and a northern group. Furthermore, there has been considerable debate about the origins of many Chinese populations and about proper assignment of these peoples to larger ethnic groups. In this paper, we suggest that dermatoglyphic data can inform these debates by helping to classify a Chinese population as a northern or southern group, using selected reference populations and quantitative methods. This study is the first to assemble and investigate dermatoglyphics from all 56 Chinese ethnic groups. It is fortunate that data on population dermatoglyphics, a field of physical anthropology, have now been collected for all 56 Chinese ethnic groups, because intermarriage between individuals from different Chinese ethnic groups occurs more frequently in recent times, making population dermatoglyphic research an ever more challenging field of inquiry.