ABSTRACT
OBJECTIVE@#To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy.@*METHODS@#U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family.@*RESULTS@#Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05).@*CONCLUSION@#Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.
Subject(s)
Humans , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Matrix Metalloproteinase 13 , Cell Line, Tumor , NF-kappa B , Multiple Myeloma/pathology , Cell Proliferation , Apoptosis , Proto-Oncogene Proteins c-bcl-2ABSTRACT
Epigallocatechin-3-gallate (EGCG), as one of the main components of green tea, has a variety of biological activities. Both in vitro and in vivo experiments widely demonstrate that EGCG has anticancer activities. The molecular mechanism of EGCG against cancer was much complicated, and EGCG suppressed tumor cell proliferation and/or induced cell apoptosis through multi-pathways. This paper reviewed the anticancer molecular mechanism of EGCG, including EGCG anti-oxidantion, prooxidation, retardant of tumor cell cycle, inhibition of tumor cell angiogenesis, inducement of cancer cell apoptosis, and regulation of microRNA, summarized the research progress of three strategies for improving bioavailability of EGCG: nano-packaging technology, synergistic application and molecular modification, and looked into research and development on anticancer activity of EGCG.
ABSTRACT
Abrin is isolated from abrin seeds (Aburs precatoriusL.), which is a kind of cytotoxic protein. This article reviewed the anticancer effect and mechanisms of Abrin from five aspects in several years, which were the molecular structure and toxicity of Abrin, the characteristics of Abrin in anticancer effect, the role of Abrin in inhibiting cancer cell proliferation, the mechanisms of Abrin induced apoptosis of cancer cells, the anticancer mechanisms of Abrin in enhancing immune function. And the application prospect of Abrin immunotoxin targeted therapy and nano preparation will be expounded in this article. It will be helpful to further research about application on Abrin. It will provide the scientific basis for discovering new drug targets of cancer.
ABSTRACT
Intravesical bacillus Calmette-Guerin (BCG) administration has been used as an adjuvant therapy after transurethral resection for superficial bladder cancer, but the exact mechanisms of its antitumor activity are not yet known. The aim of this study was to characterize the immunologic aspects of antitumor activity of BCG using an animal model. C3H/He inbred mice and murine bladder tumor cell line, MBT-2 were used. The changes in immune cells such as helper T cells, suppressor T cells, macrophages and natural killer cells in the bladder and spleen were analysed by immunohistochemical method in intravesical BCG instilled in normal bladder, MBT-2 implanted after electrocauterization of the bladder mucosa and MBT-2 implanted and intravesical BCG treated group. The changes in natural killer cell activity of the splenocytes and peritoneal lymphocytes were evaluated using 51chromium release assay at regular time intervals following intraperitoneal BCG instillation. The prophylactic anticancer effect was evaluated by observing the tumor growth in the intravesically BCG treated group after intravesical MBT-2 implantation. In immunohistochemical examination, a remarkable infiltration of macrophage and helper T cell was observed in the lamina propria of the bladder, and the helper and suppressor T cells ratio (Th/Ts ratio) was increased after intravesical BCG therapy. In 51chromium release assay, enhanced natural killer cell activity of the splenocytes and peritoneal lymphocytes was observed after intraperitoneal BCG inoculation. The growth of implanted tumor was suppressed following intravesical instillation of BCG. These results suggest that the antitumor activity of BCG is not related to the simple inflammatory reaction but to the local and systemic immune response in which helper T lymphocytes and mononuclear cells play an important role.