Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway

Zhang, Mengzhao; Du, Hongxia; Huang, Zhixin; Zhang, Pu; Yue, Yangyang; Wang, Weiyi; Liu, Wei; Zeng, Jin; Ma, Jianbin; Chen, Guanqiu; Wang, Xinyang; Fan, Jinhai

doi:10.1016/j.cbi.2018.06.013

Cited by 74 publications

(54 citation statements)

References 45 publications

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“…The mechanisms underlying the activation of caspases by TQ is very much cell type dependent. In bladder cancer cells, it has been shown that TQ induces endoplasmic reticulum (ER) stress and subsequent action of an ER-stress related signaling pathway leading to mitochondrial dysfunction and caspase 9-mediated activation of caspase 3 [108]. In leukemia-derived HL60 cells, TQ activates caspase 3 via the upstream caspase 8 and mitochondrial release of cytochrome c [105].…”

Section: Induction Of Apoptotic Cell Death In Cancer Cells By Tqmentioning

confidence: 99%

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

Gomathinayagam

Jayaraman

et al. 2020

J Cancer Prev

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Thymoquinone (TQ) is a bioactive component derived from the seeds of Nigella sativa that are commonly as black cumin. Evidences indicate that the medicinal properties of TQ have been recognized for more than 2000 years. TQ has been shown to possess potent chemopreventive properties that include anti-inflammatory and anti-neoplastic activities. Recent studies have unraveled the multiple mechanisms through which TQ exerts its chemopreventive and anticancer activity in different cancer cells in a contextual manner. The present review aims to provide a brief compendium on the molecular mechanisms through which TQ inhibits signaling pathways underlying cancer genesis, progression, and metastasis.

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Section: Induction Of Apoptotic Cell Death In Cancer Cells By Tqmentioning

confidence: 99%

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

Gomathinayagam

Jayaraman

et al. 2020

J Cancer Prev

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“…ER stress exacerbates mitochondrial dysfunction by activating caspase-9 and increasing the release of cytochrome c [18]. CHOP, DNA damage inducible gene 153 (GADD153), is the main apoptotic factor activated by ER stress, and its overexpression promotes apoptosis in cancer [19].…”

Section: Resultsmentioning

confidence: 99%

The Extracts of Artemisia absinthium L. Suppress the Growth of Hepatocellular Carcinoma Cells through Induction of Apoptosis via Endoplasmic Reticulum Stress and Mitochondrial-Dependent Pathway

Wei

Ziyayiding

et al. 2019

Molecules

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Artemisia absinthium L. has pharmaceutical and medicinal effects such as antimicrobial, antiparasitic, hepatoprotective, and antioxidant activities. Here, we prepared A. absinthium ethanol extract (AAEE) and its subfractions including petroleum ether (AAEE-Pe) and ethyl acetate (AAEE-Ea) and investigated their antitumor effect on human hepatoma BEL-7404 cells and mouse hepatoma H22 cells. The cell viability of hepatoma cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis, cell cycle, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) were analyzed by flow cytometry. The levels of proteins in the cell cycle and apoptotic pathways were detected by Western blot. AAEE, AAEE-Pe, and AAEE-Ea exhibited potent cytotoxicity for both BEL-7404 cells and H22 cells through the induction of cell apoptosis and cell cycle arrest. Moreover, AAEE, AAEE-Pe, and AAEE-Ea significantly reduced Δψm, increased the release of cytochrome c, and promoted the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) in BEL-7404 and H22 cells. AAEE, AAEE-Pe, and AAEE-Ea significantly upregulated the levels of ROS and C/EBP-homologous protein (CHOP). Further, AAEE, AAEE-Pe, and AAEE-Ea significantly inhibited tumor growth in the H22 tumor mouse model and improved the survival of tumor mice without side effects. These results suggest that AAEE, AAEE-Pe, and AAEE-Ea inhibited the growth of hepatoma cells through induction of apoptosis, which might be mediated by the endoplasmic reticulum stress and mitochondrial-dependent pathway.

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“…[33][34][35] Previous studies have confirmed that caspases and Bcl-2 family proteins, such as Bax and Bcl-2, serve important roles in the mitochondrial apoptotic pathway. [36][37][38] Mortenson et al 39 demonstrated that bortezomib triggered cell apoptosis in small cell lung cancer via decreasing Bcl-2 levels. The results of the present study revealed that nitroxoline markedly decreased the level of Bcl-2, and increased the levels of Bax, cleaved PARP and cleaved caspase-3 in a concentration-dependent manner in H929 and RPMI8226 cells.…”

Section: Discussionmentioning

confidence: 99%

BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis

Zheng

et al. 2020

Therapeutic Advances in Hematology

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Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

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Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway

Abstract: Our findings provide the first demonstration of the anticancer effect of TQ on bladder cancer, and the relationship between ER stress and mitochondrial dysfunction was clearly understood when the apoptosis progressed is revealed.

Cited by 74 publications

References 45 publications

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

The Extracts of Artemisia absinthium L. Suppress the Growth of Hepatocellular Carcinoma Cells through Induction of Apoptosis via Endoplasmic Reticulum Stress and Mitochondrial-Dependent Pathway

BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis

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