Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

Wang, Huan; Liu, Zhengyun; Gou, Ying; Qin, Yu; Xu, Yaze; Liu, Jie; Wu, Jinzhu

doi:10.2147/ijn.s83838

Cited by 45 publications

(35 citation statements)

References 26 publications

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“…A series of clinical studies and trials proved that treatment with As 2 S 2 was well tolerated, with only moderate side-effects in patients suffering from APL (13,39,40). Recent studies have also reported the potent anti-tumor properties of As 2 S 2 in various solid cancer cell lines, along with a marked reduction in cytotoxic effects in human normal cell lines (41)(42)(43). However, there have been very few studies on the anti-tumor effects of As 2 S 2 in breast cancer cells (24), and fewer studies on the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Arsenic disulfide‑induced apoptosis and its potential mechanism in two‑ and three‑dimensionally cultured human breast cancer MCF‑7 cells

et al. 2018

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In China, arsenic disulfide (As2S2) has been used for the treatment of hematological malignancies. The present study aimed to evaluate the effects of As2S2 on the human breast cancer MCF‑7 cell line cultured in both two‑dimensional (2D) monolayers and three‑dimensional (3D) spheroids to explore its therapeutic potential in breast cancer treatment. Cellular viability and the induction of apoptosis were examined with a cell counting kit‑8 (CCK‑8) assay and flow cytometric analysis, respectively. Alterations in the expression levels of apoptosis‑associated proteins, including Bcl‑2‑associated X protein (Bax), B‑cell lymphoma 2 (Bcl‑2), p53, and caspase‑7, as well as the cell survival‑associated proteins, phosphatidylinositol 3‑kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), were assessed by western blotting. Although a dose‑dependent reduction in cell viability, which occurred in association with the induction of apoptosis triggered by the addition of 2‑24 µM As2S2, was observed in both 2D‑ and 3D‑culture systems, 3D spheroids were less sensitive to the cytotoxic effect of As2S2 compared with the 2D cultured cells. A significant increase in the expression levels of Bax, p53, and caspase‑7 was observed in treated 2D‑cultured cells, whereas a similar increase in the expression levels of Bax was only confirmed in treated 3D spheroids, although there was a trend towards the increased expression of p53 and caspase‑7 in the 3D spheroids. These results suggested that these molecules are closely associated with As2S2‑mediated cytotoxicity in the two culture systems, and further suggested that the difference in the sensitivity to As2S2 between 2D monolayers and 3D spheroids may be attributed to the differential alterations in the expression levels of proteins associated with cell mortality. Significant downregulation of the expression levels of Bcl‑2, PI3K, Akt and mTOR was observed in the two culture systems. Taken together, the results of the present study demonstrated that As2S2 inhibits cell viability and induces apoptosis in both 2D‑ and 3D‑ cultured MCF‑7 cells, which may be associated with activation of the pro‑apoptotic pathway and the inhibition of pro‑survival signaling. These results have provided novel insights into clinical applications of As2S2 in the treatment of patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

Arsenic disulfide‑induced apoptosis and its potential mechanism in two‑ and three‑dimensionally cultured human breast cancer MCF‑7 cells

et al. 2018

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“…Several reports about ultrafine particulate matter-induced necrotic cell death have been published. 32 Necrosis induced by QDs 33,34 has also been found, while necroptosis has not been reported.…”

Section: Necrosismentioning

confidence: 99%

“…26 Similar to cadmium-containing QDs, other types of QDs have similar effects on apoptosis. 34,35 It was generally acknowledged that apoptosis usually takes place through mitochondrial or death receptor pathway with respective activation of caspase 9 and caspase 8. Initiation of extrinsic pathway by stimulation of QDs was attributed to release of tumor necrosis factor-α or contact of Fas ligand with Fas receptor.…”

Section: Apoptosismentioning

confidence: 99%

“…Lipid peroxidation of membrane and liberation of substrates would occur when the buffering system is extremely collapsed. Leakage of several classes of proteases from the ruptured organelles is responsible for the observed cell death, for example, Ca 2+ from the ER, 34 mitochondrial DNA from the mitochondria 70 or cathepsin from the disrupted lysosome, 71 which were authenticated by several studies with different types of cells. However, contributions of certain physicochemical property to the impairment of organelles are not completely explained.…”

Section: Disturbance Of Subcellular Structuresmentioning

confidence: 99%

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Dysfunction of various organelles provokes multiple cell death after quantum dot exposure

Wang

Tang

2018

IJN

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Quantum dots (QDs) are different from the materials with the micrometer scale. Owing to the superiority in fluorescence and optical stability, QDs act as possible diagnostic and therapeutic tools for application in biomedical field. However, potential threats of QDs to human health hamper their wide utilization in life sciences. It has been reported that oxidative stress and inflammation are involved in toxicity caused by QDs. Recently, accumulating research unveiled that disturbance of subcellular structures plays a magnificent role in cytotoxicity of QDs. Diverse organelles would collapse during QD treatment, including DNA damage, endoplasmic reticulum stress, mitochondrial dysfunction and lysosomal rupture. Different forms of cellular end points on the basis of recent research have been concluded. Apart from apoptosis and autophagy, a new form of cell death termed pyroptosis, which is finely orchestrated by inflammasome complex and gasdermin family with secretion of interleukin-1 beta and interleukin-18, was also summarized. Finally, several potential cellular signaling pathways were also listed. Activation of Toll-like receptor-4/myeloid differentiation primary response 88, nuclear factor kappa-light-chain-enhancer of activated B cells and NACHT, LRR and PYD domains-containing protein 3 inflammasome pathways by QD exposure is associated with regulation of cellular processes. With the development of QDs, toxicity evaluation is far behind its development, where specific mechanisms of toxic effects are not clearly defined. Further studies concerned with this promising area are urgently required.

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“…Ki-67, a nuclear protein, is widely used as a tumour proliferation marker. Our study showed that the A previous study showed that cell apoptosis may be induced by ER stress and mitochondrial membrane permeability [27,28]. CHOP, a key protein of ER stress-mediated cell death, also known as a bZIPcontaining transcription factor, targets many apoptotic genes, including NOXA, modifying their expression and ultimately resulting in apoptosis [29].…”

Section: Discussionmentioning

confidence: 53%

Lithium Chloride Induces Apoptosis in Human Choroidal Melanoma Cells via the NOXA/Mcl-1 Axis and Induction of ER Stress

Zhang¹,

Zhang²,

Li³

et al. 2020

Preprint

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Background: Choroidal melanoma is the most common primary intraocular malignancy that occurs in adults. Lithium chloride (LiCl) has been safely used in the clinic to treat psychiatric disorders for several decades. In this study, we aimed to understand whether LiCl exerts anticancer effects on choroidal melanoma cells and elucidate the underlying molecular mechanisms. Methods: Human choroidal melanoma cells were treated with LiCl, and cell survival was assessed with MTT assays. Cell proliferation was measured by plate colony formation assays. Cell apoptosis was evaluated using flow cytometry, and proteins were detected using western blotting. A human choroidal melanoma xenograft model was established to demonstrate the effect of LiCl on human choroidal melanoma in vivo. An unpaired t-test was used to compare differences between two groups, and one-way ANOVA was used to compare differences among more than two groups.Results: We found that LiCl inhibited cell survival and clonogenic potential and induced apoptosis in human choroidal melanoma cells. LiCl also reduced the proliferation of choroidal melanoma cells in vivo. Moreover, the upregulation of NOXA and downregulation of Mcl-1 were responsible for LiCl-induced apoptosis. Mcl-1 overexpression obviously impaired LiCl-induced apoptosis and cleavage of casp8, casp9, casp3 and PARP. Moreover, the protein expression of endoplasmic reticulum stress markers, including IRE1α, Bip, p-eIF2α, ATF4 and CHOP, was upregulated following treatment with LiCl. Conclusions: In summary, LiCl induced an endoplasmic reticulum stress response while activating intrinsic apoptosis. Furthermore, the NOXA/Mcl-1 axis contributed to LiCl-induced apoptosis both in vitro and in vivo. The present study provides important mechanistic insight into potential cancer treatments involving LiCl and enhances the understanding of human choroidal melanoma.

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Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

Cited by 45 publications

References 26 publications

Arsenic disulfide‑induced apoptosis and its potential mechanism in two‑ and three‑dimensionally cultured human breast cancer MCF‑7 cells

Arsenic disulfide‑induced apoptosis and its potential mechanism in two‑ and three‑dimensionally cultured human breast cancer MCF‑7 cells

Dysfunction of various organelles provokes multiple cell death after quantum dot exposure

Lithium Chloride Induces Apoptosis in Human Choroidal Melanoma Cells via the NOXA/Mcl-1 Axis and Induction of ER Stress

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