Cantharidin Inhibits Anti-Apoptotic Bcl-2 Family Proteins and Induces Apoptosis in Human Osteosarcoma Cell Lines MG-63 and MNNG/HOS via Mitochondria-Dependent Pathway

Feng, Shoumin; Zhu, Jian; Xia, Kaishun; Yu, Wei; Wang, Yitian; Wang, Junjie; Li, Fangcai; Zhang, Yang; Yang, Xiaobo; Liu, Bing; Tao, Huimin; Liang, Chengzhen

doi:10.12659/msm.910294

Cited by 16 publications

(10 citation statements)

References 38 publications

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“…Liu et al reported that dysregulation of the ezrin/NF-κB signal pathway can activate epithelial-mesenchymal transition (EMT) in osteosarcoma, thus contributing to cancer progression and metastasis [25]. Designing the drugs or treatment methods specific to the genetic mutations in tumorigenesis may provide novel therapeutic methods for osteosarcoma [26]. Recently, a variety of molecular markers and therapeutic targets have been confirmed for osteosarcoma, including miRNAs, lncRNAs, and some specific genes.…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporter 4 (MCT4) Overexpression Is Correlated with Poor Prognosis of Osteosarcoma

et al. 2019

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Background Monocarboxylate transporter 4 (MCT4) is a critical element for glycolytic metabolism and malignant behaviors in many tumor cells. This study aimed to determine the expression level of MCT4 protein and its prognostic value in osteosarcoma. Material/Methods MCT4 expression was detected via immunohistochemical and Western blot analysis for 100 osteosarcoma patients. The correlation between MCT4 expression and clinical factors among the patients was analyzed using the chi-square test. Overall survival of osteosarcoma patients was estimated by Kaplan-Meier analysis. The prognostic value of MCT4 was evaluated using Cox regression analysis with adjustments for clinicopathological variables. Results MCT4 expression was significantly upregulated in osteosarcoma tissues compared with that in adjacent normal ones, detected via both immunohistochemical and Western blot analyses. High MCT4 expression showed a positive association with distant metastasis ( P =0.000) and recurrence ( P =0.000) of osteosarcoma. Kaplan-Meier analysis indicated that overall survival of osteosarcoma patients was significantly higher in the low MCT4 expression group than in the high expression group (log-rank test, P <0.001). Multivariate analysis indicated that MCT4 expression and clinical stage, which are tightly related to the prognosis of osteosarcoma, might be independent predictors of osteosarcoma prognosis. Conclusions High MCT4 expression appears to contribute to osteosarcoma progression and the upregulation of MCT4 may predict poor prognosis among osteosarcoma patients.

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Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporter 4 (MCT4) Overexpression Is Correlated with Poor Prognosis of Osteosarcoma

et al. 2019

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“…Conditions that disrupt intracellular balance, such as mitochondrial dysfunction, calcium imbalance, and DNA mutation, can activate the intrinsic apoptotic pathway, which is mainly composed of and regulated by members of the multidomain B cell lymphoma 2 (Bcl-2) family (Shukla et al, 2017;Jin et al, 2018). This family includes the antiapoptotic molecules Bcl-2 and Bcl-XL (Perciavalle et al, 2012;Wen-Juan et al, 2012;Feng et al, 2018) and the proapoptotic molecules Bcl-2-related X protein (Bax) and BCL-2 antagonist (Bak) (Hsu et al, 1997;Mathai et al, 2005), among others. The intrinsic pathway is activated mainly by the interaction of Bcl-2-like protein 11 (BCL2L11, also known as Bim) or BH3-interacting domain death agonist (Bid) with Bax or Bak.…”

Section: Apoptotic Mechanismmentioning

confidence: 99%

Regulation of Apoptosis by Enteroviruses

et al. 2020

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Enterovirus infection can cause a variety of diseases and severely impair the health of humans, animals, poultry, and other organisms. To resist viral infection, host organisms clear infected cells and viruses via apoptosis. However, throughout their long-term competition with host cells, enteroviruses have evolved a series of mechanisms to regulate the balance of apoptosis in order to replicate and proliferate. In the early stage of infection, enteroviruses mainly inhibit apoptosis by regulating the PI3K/ Akt pathway and the autophagy pathway and by impairing cell sensors, thereby delaying viral replication. In the late stage of infection, enteroviruses mainly regulate apoptotic pathways and the host translation process via various viral proteins, ultimately inducing apoptosis. This paper discusses the means by which these two phenomena are balanced in enteroviruses to produce virus-favoring conditions-in a temporal sequence or through competition with each other. This information is important for further elucidation of the relevant mechanisms of acute infection by enteroviruses and other members of the picornavirus family.

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“…Overexpression and mutations in the BCL2 gene are correlated with cancer development, and BCL2 upregulation has been reported in several types of cancers [65][66][67]. Furthermore, the correlation between BCL2 inhibition and apoptosis inducement has been reported by various studies [68][69][70]. The combination of MTX and Que down-regulated BCL2 significantly, accelerating apoptosis inducement.…”

Section: Discussionmentioning

confidence: 93%

Quercetin and Methotrexate in Combination have Anticancer Activity in Osteosarcoma Cells and Repress Oncogenic MicroRNA-223

et al. 2022

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Introduction Osteosarcoma (OS) is one of the most common bone neoplasms in adolescents. Notable short- and long-term toxic effects of OS chemotherapy regimens have been reported. Hence, new chemotherapeutic agents with the ability to potentiate OS chemotherapy drugs and protect non-tumorous tissues are required. Methods Saos-2 cells were treated with Methotrexate (MTX) and Quercetin (Que) (a polyphenolic flavonoid with anti-tumor effects) alone and in combination. MTT assay was performed to investigate the cytotoxicity of the drugs. Moreover, apoptosis-involved genes, including miR-223, p53, BCL-2, CBX7, and CYLD expression were analyzed via qRT-PCR. Annexin V-FITC/PI kit was employed to assess the apoptosis rate. Results The MTT results showed that Que increases MTX cytotoxicity on OS cells. The measured IC50s are 142.3 µM for QUE and 13.7 ng/ml for MTX. A decline in MTX IC50 value was observed from 13.7 ng/ml to 8.45 ng/ml in the presence of Que. Moreover, the mRNA expression outcomes indicated that the combination therapy significantly up-regulates the tumor suppressor genes, such as p53, CBX7, and CYLD, and declines anti-apoptotic genes BCL-2 and miR-223, which can lead to proliferation inhibition and apoptosis inducement. Furthermore, the apoptosis rate increased significantly from 6.03% in the control group to 38.35% in Saos-2 cells that were treated with the combination of MTX and Que. Conclusion Que, with the potential to boost the anticancer activity of MTX on Saos-2 cancer cells through proliferation inhibition and apoptosis induction, is a good candidate for combination therapy.

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Cantharidin Inhibits Anti-Apoptotic Bcl-2 Family Proteins and Induces Apoptosis in Human Osteosarcoma Cell Lines MG-63 and MNNG/HOS via Mitochondria-Dependent Pathway

Cited by 16 publications

References 38 publications

Monocarboxylate Transporter 4 (MCT4) Overexpression Is Correlated with Poor Prognosis of Osteosarcoma

Monocarboxylate Transporter 4 (MCT4) Overexpression Is Correlated with Poor Prognosis of Osteosarcoma

Regulation of Apoptosis by Enteroviruses

Quercetin and Methotrexate in Combination have Anticancer Activity in Osteosarcoma Cells and Repress Oncogenic MicroRNA-223

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