Dataset Information

Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

ABSTRACT: Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherapeutic agents that can be safely administered to patients is a very important research issue. Therefore, this study investigated whether tangeretin can induce apoptosis and identified the signaling pathways of tangeretin-induced apoptosis in human bladder cancer cells using two-dimensional gel electrophoresis (2DGE). The results of the study demonstrated that 60 ?M tangeretin reduced the cell survival of a BFTC-905 bladder carcinoma cell line by 42%, and induced early and late apoptosis in the cells. In this study 2DGE proteomics technology identified 41 proteins that were differentially-expressed in tangeretin-treated cells, and subsequently LC?MS/MS analysis was performed to identify the proteins. Based on the functions of the differentially-expressed proteins, the results suggested that tangeretin caused mitochondrial dysfunction and further induced apoptosis in bladder cancer cells. Moreover, western blotting analysis demonstrated that tangeretin treatment disturbed calcium homeostasis in the mitochondria, triggered cytochrome C release, and activated caspase-3 and caspase-9, which led to apoptosis. In conclusion, our results showed that tangeretin-induced apoptosis in human bladder cancer cells is mediated by mitochondrial inactivation, suggesting that tangeretin has the potential to be developed as a new drug for the treatment of bladder cancer.

SUBMITTER: Lin JJ

PROVIDER: S-EPMC6429142 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

Lin Jen-Jie JJ Huang Chun-Chieh CC Su Yu-Li YL Luo Hao-Lun HL Lee Nai-Lun NL Sung Ming-Tse MT Wu Yu-Jen YJ

International journal of molecular sciences 20190226 5

Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherap ...[more]

PMID: 30813616

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Project description:Ovarian carcinoma (OC) patients encounter the severe challenge of clinical management owing to lack of screening measures, chemoresistance and finally dearth of non-toxic therapeutics. Cancer cells deploy various defense strategies to sustain the tumor microenvironment, among which deregulated apoptosis remains a versatile promoter of cancer progression. Although recent research has focused on identifying agents capable of inducing apoptosis in cancer cells, yet molecules efficiently breaching their survival advantage are yet to be classified. Here we identify lectin, Sambucus nigra agglutinin (SNA) to exhibit selectivity towards identifying OC by virtue of its specific recognition of ?-2, 6-linked sialic acids. Superficial binding of SNA to the OC cells confirm the hyper-sialylated status of the disease. Further, SNA activates the signaling pathways of AKT and ERK1/2, which eventually promotes de-phosphorylation of dynamin-related protein-1 (Drp-1). Upon its translocation to the mitochondrial fission loci Drp-1 mediates the central role of switch in the mitochondrial phenotype to attain fragmented morphology. We confirmed mitochondrial outer membrane permeabilization resulting in ROS generation and cytochrome-c release into the cytosol. SNA response resulted in an allied shift of the bioenergetics profile from Warburg phenotype to elevated mitochondrial oxidative phosphorylation, altogether highlighting the involvement of mitochondrial dysfunction in restraining cancer progression. Inability to replenish the SNA-induced energy crunch of the proliferating cancer cells on the event of perturbed respiratory outcome resulted in cell cycle arrest before G2/M phase. Our findings position SNA at a crucial juncture where it proves to be a promising candidate for impeding progression of OC. Altogether we unveil the novel aspect of identifying natural molecules harboring the inherent capability of targeting mitochondrial structural dynamics, to hold the future for developing non-toxic therapeutics for treating OC.

Dataset Information

Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

Publications

Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

Similar Datasets

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