Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanisms by which BBR repressed the metastatic potential of breast cancer cells. BBR was found to downregulate the enzymatic activities and expression levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the Akt/nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways. Furthermore, BBR repressed the expression of the Akt protein by modulating the mRNA expression level and protein degradation of Akt. In conclusion, this study suggests that BBR can reduce the metastatic potential of highly metastatic breast cancer cells and may be a useful adjuvant therapeutic agent in the treatment of breast cancer by targeting the Akt pathway.
Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.
The availability of adequate cancer stem cells or cancer stem-like cell (CSC) is important in cancer study. From ovarian cancer cell lines, SKOV3 and OVCAR3, we induced peritoneal ascites tumors in immunodeficient mice. Among the cells (SKOV3.PX1 and OVCAR3.PX1) from those tumors, we sorted both CD44 and CD133 positive cells (SKOV3.PX1_133+44+, OVCAR3.PX1_133+44+), which manifest the characteristics of self-renewal, multi-lineage differentiation, chemoresistance and tumorigenicity, those of cancer stem-like cells (CSLC). Intraperitoneal transplantation of these CD44 and CD133 positive cells resulted in poorer survival in the engrafted animals. Clinically, increased CD133 expression was found in moderately and poorly differentiated (grade II and III) ovarian serous cystadenocarcinomas. The ascites tumor cells from human ovarian cancers demonstrated more CD133 and CD44 expressions than those from primary ovarian or metastatic tumors and confer tumorigenicity in immunodeficient mice. Compared to their parental cells, the SKOV3.PX1_133+44+ and OVCAR3.PX1_133+44+ cells uniquely expressed 5 CD markers (CD97, CD104, CD107a, CD121a, and CD125). Among these markers, CD97, CD104, CD107a, and CD121a are significantly more expressed in the CD133+ and CD44+ double positive cells of human ovarian ascites tumor cells (Ascites_133+44+) than those from primary ovarian or metastatic tumors. The cancer stem-like cells were enriched from 3% to more than 70% after this manipulation. This intraperitoneal enrichment of cancer stem-like cells, from ovarian cancer cell lines or primary ovarian tumor, potentially provides an adequate amount of ovarian cancer stem-like cells for the ovarian cancer study and possibly benefits cancer therapy.
Ganoderma is classified as a top grade traditional Chinese medicine for promoting human health by regulating 'vital energy'. Its potency towards metabolism and energy homeostasis, particularly, metabolic adaptations of adipocytes, needs to be re-evaluated through an evidence-based study. Here, the triterpenoid-rich Ganoderma tsugae ethanol extract (GTEE) was found to contribute towards adipogenesis accompanied with elevated intracellular lipid metabolic flux. Additionally, proteomic profiling revealed GTEE-upregulated mitochondrial remodeling and chemical energy redox modifications, which display UCP1-positive browning fat-selective features and a NADH-mediated adaptive mechanism. GTEE-treated mice with diet-induced obesity also resulted in the amelioration of white adipocyte hypertrophy and the appearance of UCP1-positive browning adipocytes. Our novel findings unravel that GTEE could promote intracellular metabolic flexibility and plasticity followed by the induction of adipocyte browning.
Blood cysts are benign tumors in nature and seldom need surgical removal. Herein, we report an 86-year-old patient with a blood cyst originating from the fossa ovalis accompanied by an atrial septal defect. The patient used the bizarre sleeping postures, including prostrating and worshiping, to relieve chest tightness. The septal base defect kept the tumor progressively enlarged with time, which contributed to a "ball-valve "effect and caused tricuspid flow obstruction. It was resolved after excision. This case report emphasizes that long-term follow-up and increased awareness are required for unpredictable intracardiac blood cyst development.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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