Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production

Chen, Yen Chou; Shen, Shing Chuan; Lee, William R.; Hsu, Foun Lin; Lin, Hui Yi; Ko, Ching Huai; Tseng, Shi Wen

doi:10.1016/s0006-2952(02)01386-2

Cited by 213 publications

(136 citation statements)

References 42 publications

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“…It is well known that caspase-8 and caspase-9 are essential proteases of extrinsic and intrinsic apoptotic pathways (Chen et al, 2014). Reports showed that the intrinsic apoptosis pathway is characterized as mitochondrial dysfunction and stimulation of caspase-9 and caspase-3 and caspase-3 is the cuultimate executioner for the nucleic changes with apoptosis (Chen et al, 2002). Therefore, mitochondrial damage is associated with the high level of caspase-9 and caspase-3.…”

Section: Discussionmentioning

confidence: 99%

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Gao

Wu²,

Zeng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteen repeats in the classical Armadillo family members. Materials and Methods: In the study, we explore the biological functions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performed with SK-BR3 and MCF-7 cell lines. Cell proliferation and colony formation assays, along with flow cytometry, were carried out to evaluate the roles of ALEX1. Results: ALEX1 overexpression in SK-BR3 breast cancer cells inhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cells increased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression of ALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochrome c, active caspase-9 and active caspase-3 and down-regulating the levels of Bcl-2 and mitochondria cytochrome c. Simultaneouly, silencing of ALEX1 inhibited intrinsic apoptosis cascades through down-regulating the expression of Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 and mitochondria cytochrome c. Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor gene has been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidate therapeutic target.

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Section: Discussionmentioning

confidence: 99%

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Gao

Wu²,

Zeng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…In this study, we found that KDR-siRNA treatment decreased the Bcl-2 to Bax ratio in MCF-7 cells, increased mitochondrial membrane permeability, induced the release of cytochrome c, increased the expression of Apaf-1, and increased the protein level and activity of cleaved caspase-3. Because caspase-3 is the ultimate executioner caspase essential for the nucleic changes associated with apoptosis [26], it is reasonable to infer that the elevated level of activated caspase-3 is responsible for the increased apoptosis in MCF-7 cells. The role of caspase activation in KDR-siRNA-induced apoptosis was further confirmed by the prevention of KDR-siRNA-induced apoptosis in MCF-7 cells through pretreatment with the caspase inhibitor Z-VAD-FMK.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of KDR expression induces apoptosis in breast cancer cells

Zhang

Yan

et al. 2014

Cellular and Molecular Biology Letters

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Angiogenesis plays a crucial role in the growth, invasion and metastasis of breast cancer. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are the key regulators of tumor angiogenesis. VEGFR-2, known as the kinase insert domain receptor (KDR), is a key receptor involved in malignant angiogenesis. We previously showed that knocking down KDR with short interference RNA (KDR-siRNA) markedly decreased KDR expression and suppressed tumor growth in a xenograft model. However, the mechanisms underlying the anti-cancer effects of KDR-siRNA are not clearly understood. This study aimed to elucidate the molecular mechanisms that induce apoptosis in human breast cancer MCF-7 cells after transfection with KDRsiRNA. We studied the effects of KDR-siRNA on proliferation, apoptosis, antiapoptotic and pro-apoptotic proteins, mitochondrial membrane permeability, cytochrome c release and caspase-3 activity. The results indicated that KDRsiRNA treatment significantly inhibited the proliferation and induced the apoptosis of MCF-7 cells, reduced the levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xl, and increased the level of the pro-apoptotic protein Bax, resulting in a decreased Bcl-2/Bax ratio. KDR-siRNA also enhanced the mitochondrial membrane permeability, induced cytochrome c release from the mitochondria, upregulated apoptotic protease-activating factor-1 (Apaf-1), cleaved caspase-3, and increased caspase-3 activity in MCF-7 cells. Furthermore, KDR-siRNA-induced apoptosis in MCF-7 cells was blocked by the caspase inhibitor Z-VAD-FMK, suggesting a role of caspase activation in the induction of apoptosis. These results indicate that the Bcl-2 family proteins and caspase-related mitochondrial pathways are primarily involved in KDR-siRNAinduced apoptosis in MCF-7 cells and that KDR might be a potential therapeutic target for human breast cancer treatments.

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“…Emodin has been previously reported to possess antiviral [16], antiinflammatory [17], antiulcerogenic [18], immunosuppressive [19], and chemopreventive activities [20]. Interestingly, antiproliferative effects of emodin have been observed in many tumor cell lines, including HER2/neuoverexpressing breast cancer [21], lung cancer [22], leukemia [23], HCC [24], and neuroblastoma [25] but not in normal cells, suggesting that emodin may have a significant therapeutic efficacy as an anticancer agent. Emodin exerts its pleiotropic anti-cancer effects through diverse mechanisms including the activation of caspase-3 [23] and upregulation of p53 and p21 [26].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, antiproliferative effects of emodin have been observed in many tumor cell lines, including HER2/neuoverexpressing breast cancer [21], lung cancer [22], leukemia [23], HCC [24], and neuroblastoma [25] but not in normal cells, suggesting that emodin may have a significant therapeutic efficacy as an anticancer agent. Emodin exerts its pleiotropic anti-cancer effects through diverse mechanisms including the activation of caspase-3 [23] and upregulation of p53 and p21 [26]. Moreover, emodin has been reported to inhibit the kinase activity/activation of p56lck, HER2/neu [21], casein kinase [27], NF-jB [28], activator protein 1 [29,30], AKT [30], matrix metalloproteinases [29,31], and the expression of chemokine receptor CXCR4 [32].…”

Section: Introductionmentioning

confidence: 99%

An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins

et al. 2013

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Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently under clinical trials for cancer, however many tumor cells, including hepatocellular carcinoma (HCC) develop resistance to TRAIL-induced apoptosis. Hence, novel agents that can alleviate TRAIL-induced resistance are urgently needed. In the present report, we investigated the potential of emodin to enhance apoptosis induced by TRAIL in HCC cells. As observed by MTT cytotoxicity assay and the externalization of the membrane phospholipid phosphatidylserine, we found that emodin can significantly potentiate TRAIL-induced apoptosis in HCC cells. When investigated for the mechanism(s), we observed that emodin can downregulate the expression of various cell survival proteins, and induce the cell surface expression of both TRAIL receptors, death receptors (DR) 4 as well as 5. In addition, emodin increased the expression of C/EBP homologous protein (CHOP) in a time-dependent manner. Knockdown of CHOP by siRNA decreased the induction of emodin-induced DR5 expression and apoptosis. Emodin-induced induction of DR5 was mediated through the generation of reactive oxygen species (ROS), as N-acetylcysteine blocked the induction of DR5 and the induction of apoptosis. Also, the knockdown of X-linked inhibitor of apoptosis protein by siRNA significantly reduced the sensitization effect of emodin on TRAILinduced apoptosis. Overall, our experimental results clearly indicate that emodin can indeed potentiate TRAIL-induced Aruljothi Subramaniam and Ser Yue Loo contributed equally to this work.

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Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production

Cited by 213 publications

References 42 publications

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Downregulation of KDR expression induces apoptosis in breast cancer cells

An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins

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