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Potential Anticancer Properties and Mechanisms of Action of Formononetin.
Jiang, D, Rasul, A, Batool, R, Sarfraz, I, Hussain, G, Mateen Tahir, M, Qin, T, Selamoglu, Z, Ali, M, Li, J, et al
BioMed research international. 2019;:5854315
Abstract
Nature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from Trifolium pratense, Glycine max, Sophora flavescens, Pycnanthus angolensis, and Astragalus membranaceus. Formononetin has been well-documented for its anti-inflammatory, anticancer, and antioxidant properties. Recently anticancer activity of formononetin is widely studied. This review aims to highlight the pharmacological potential of formononetin, thus providing an insight of its status in cancer therapeutics. Formononetin fights progression of cancer via inducing apoptosis, arresting cell cycle, and halting metastasis via targeting various pathways which are generally modulated in several cancers. Although reported data acclaims various biological properties of formononetin, further experimentation on mechanism of its action, medicinal chemistry studies, and preclinical investigations are surely needed to figure out full array of its pharmacological and biological potential.
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A novel fluorinated thiosemicarbazone derivative- 2-(3,4-difluorobenzylidene) hydrazinecarbothioamide induces apoptosis in human A549 lung cancer cells via ROS-mediated mitochondria-dependent pathway.
Zhao, Y, Guo, C, Wang, L, Wang, S, Li, X, Jiang, B, Wu, N, Guo, S, Zhang, R, Liu, K, et al
Biochemical and biophysical research communications. 2017;(1):65-71
Abstract
Thiosemicarbazone, a class of compounds with excellent biological activity, especially antitumor activity, have attracted wide attention. In this study, a novel fluorinated thiosemicarbazone derivative, 2-(3,4-difluorobenzylidene) hydrazinecarbothioamide (compound 1) was synthesized and its antitumor activities were further investigated on a non-small cell lung cancer cell line (A549) along with its underlying mechanisms. Compound 1 showed significant anti-proliferative activity on A549 cells, which was further proved by colony formation experiment. Compound 1 also inhibits the invasion of A549 cells in a trans-well culture system. Moreover, compound 1 markedly induced apoptosis on A549 cells, and the ratio of Bcl-2/Bax was decreased while the amount of p53, Cleaved-Caspase 3 and Cleaved-PARP expression were increased significantly. Compound 1 decreased the mitochondrial membrane potential, while the content of reactive oxygen was increased obviously. It is revealed that compound 1 mediated cell cycle arrest in G0/G1 phase by reducing G1 phase dependent proteins, CDK4 and Cyclin D1. As a result, it is indicated that compound 1 induced apoptosis on A549 cells was realized by regulating ROS-mediated mitochondria-dependent signaling pathway.
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Role of the Wilms' tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms.
Li, Y, Wang, J, Li, X, Jia, Y, Huai, L, He, K, Yu, P, Wang, M, Xing, H, Rao, Q, et al
Oncology reports. 2014;(6):2680-6
Abstract
The Wilms' tumor 1 (WT1) gene is one of the regulating factors in cell proliferation and development. It is a double-functional gene: an oncogene and a tumor suppressor. This gene was found to be highly expressed in many leukemic cell lines and in patients with acute myeloid leukemia. In the present study, we demonstrated that the WT1 gene was commonly expressed in leukemic cell lines apart from U937 cells. The K562 cell line which expresses WT1 at a high level (mRNA and protein) was used in the entire experiment. By MTT and colony formation assays, we found that curcumin, an inhibitor of the WT1 protein, inhibited cell proliferation and clonogenicity in a time- and dose-dependent manner. It also caused cell cycle arrest at the G2/M phase. We then designed specific short hairpin RNAs (shRNAs) which could downregulate WT1 by 70-80% at the mRNA and protein levels. Reduction in the WT1 levels attenuated the proliferative ability and clonogenicity. Cell cycle progression analysis indicated that the proportion of cells in the G0/G1 phase increased while the proportion in the S phase decreased distinctively. ChIP-DNA selection and ligation (DSL) experiment identified a cohort of genes whose promoters are targeted by WT1. These genes were classified into different cellular signaling pathways using MAS software and included the Wnt/β-catenin pathway, MAPK signaling pathway, apoptosis pathway, and the cell cycle. We focused on the Wnt/β-catenin signaling pathway, and compared expression of several genes in the K562 cells transfected with the control shRNA and WT1-specific shRNA. β-catenin, an important gene in the Wnt canonical pathway, was downregulated after WT1 RNAi. Target genes of β-catenin which participate in cell proliferation and cell cycle regulation, such as CCND1 and MYC, were also significantly downregulated. Collectively, these data suggest that WT1 functions as an oncogene in leukemia cells, and one important mechanism is regulation of the Wnt/β-catenin pathway.
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[Effect of arsenic trioxide combined with adriamycin on the proliferation and apoptosis of human lymphoma cells].
Huang, R, Li, X, Huang, X, Yang, X, Li, W
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2009;(6):515-22
Abstract
OBJECTIVE To determine the effect of arsenic trioxide combined with adriamycin(ADM) on the proliferation and apoptosis of human lymphoma cells. METHODS Raji cells were divided into an experimental group and a control group, and the experimental group was further divided into 1 micromol/L As(2)O(3) group,2 micromol/L As(2)O(3) group, ADM group,1 micromol/L As(2)O(3) and ADM group,2 micromol/L As(2)O(3) and ADM group. Human lymphoma cells Raji were treated with As(2)O(3) combined with ADM. Wright-Giemsa dying assay was used to observe the apoptosis morphology of lymphoma cells. The proliferation of the cells treated with As(2)O(3) and adriamycin was detected by the method of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT). Flow cytometry(FCM) was used to detect the apoptosis rate of lymphoma and the fluorescene density in the lymphocytes. Effect of arsenic trioxide and adriamycin on the mutant p53 expression in Raji cells was detected by semi-quantitive RT-PCR. RESULTS Evident apoptotic morphological changes of Raji cells were observed 24 hours after treatment with As(2)O(3) or ADM. Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the inhibition ratio significantly (P<0.05), and the inhibition rate was related to the concentration and action time of As(2)O(3) (P<0.05). Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the apoptosis rate of lymphoma cells with obvious difference (P<0.05). Semi-quantitive and RT-PCR showed that the expression of mutant p53 in As(2)O(3) and ADM alone and combined groups was obviously less than that in the control (P<0.05). After the treatment with 1 micromol/L and 2 micromol/L As(2)O(3), the fluorescene density in the Raji cells was 18.53 and 18.12, 0.056 and 0.023 times increase respectively.There was no difference (P>0.05). CONCLUSION As(2)O(3) and ADM alone or combined can inhibit the proliferation, induce cell apoptosis, and downregulate the expression of mutant p53 in vitro. As(2)O(3) combined with ADM has synergistic anti-lymphoma cell effect in vitro. As(2)O(3) has no significant effect on the concentration of ADM on the Raji cells, but can enhance the chemosensitivity of Raji cells, and its mechanism may be that it can downregulate the expression of mutant p53.