Loperamide overcomes the resistance of colon cancer cells to bortezomib by inducing CHOP-mediated paraptosis-like cell death

Kim, In Young; Shim, Min June; Lee, Dong Min; Lee, A. Reum; Kim, Mi Ae; Yoon, Mi Jin; Kwon, Man Jae; Lee, Hae-In; Seo, Min Ji; Choi, Yong Won; Choi, Kyeong Sook

doi:10.1016/j.bcp.2018.12.006

Cited by 22 publications

(24 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During this process, they disrupt Ca 2+ homeostasis at the ER by altering Ca 2+ store content and Ca 2+ dynamics (including the uptake, release, and leakage of Ca 2+ ) and/or at the mitochondria by affecting the activities of MCU complex components to regulate the mitochondrial Ca 2+ levels. In addition, recent studies have shown that treatment of cancer cells with drugs that perturb Ca 2+ homeostasis [CGP-37157 (Yoon et al, 2012), lercanidipine (Lee et al, 2019), and loperamide (Kim et al, 2019)] or Nutlin-3, which is a chemical that triggers the mitochondrial unfolded protein response (mtUPR) (Lee et al, 2017), induces paraptosis when…”

Section: Paraptosis-inducing Agents Associated With Ca 2+ Imbalancementioning

confidence: 99%

“…Loperamide + Proteasome Inhibitor Kim et al (2019) showed that the widely used anti-diarrheal drug, loperamide (Lop), effectively enhances the cytotoxicity of PIs in various colon cancer cells, but not in normal colon epithelial cells (Kim et al, 2019). The combination of sublethal concentrations of Btz and Lop (Lop/Btz) effectively triggered paraptosis-like cell death accompanied by severe vacuolation derived from the ER in various colon cancer cells, whereas either agent alone failed to induce notable vacuolation or cell death.…”

Section: Lercanidipine + Proteasome Inhibitormentioning

confidence: 99%

“…The term "paraptosis-like cell death" has been used to describe the types of cell death accompanied by the dilation of either the mitochondria or the ER alone or those that do not share multiple biochemical features of paraptosis, including the activation of MAP kinases, the downregulation of AIP-1/Alix, and the inhibition of vacuolation and cell death by cycloheximide, etc. (Zhang et al, 2010;Xue et al, 2018;Kim et al, 2019). Recently, Ca 2+ depletion in the ER and the subsequent mitochondrial Ca 2+ overload have been shown to play a critical role in the paraptosis induced by various natural products and chemicals (Yoon et al, 2012(Yoon et al, , 2014Yumnam et al, 2016;Kim et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…(Zhang et al, 2010;Xue et al, 2018;Kim et al, 2019). Recently, Ca 2+ depletion in the ER and the subsequent mitochondrial Ca 2+ overload have been shown to play a critical role in the paraptosis induced by various natural products and chemicals (Yoon et al, 2012(Yoon et al, , 2014Yumnam et al, 2016;Kim et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

Kim

Lee

Seo

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Since paraptosis is morphologically and biochemically different from apoptosis, understanding its regulatory mechanisms may provide a novel therapeutic strategy in malignant cancer cells that have proven resistant to conventional pro-apoptotic treatments. Relatively little is known about the molecular basis of paraptosis, but perturbations of cellular proteostasis and ion homeostasis appear to critically contribute to the process. Ca2+ transport has been shown to be important in the paraptosis induced by several natural products, metal complexes, and co-treatment with proteasome inhibitors and certain Ca2+-modulating agents. In particular, the Ca2+-mediated communication between the ER and mitochondria plays a crucial role in paraptosis. Mitochondrial Ca2+ overload from the intracellular Ca2+-flux system located at the ER–mitochondrial axis can induce mitochondrial dilation during paraptosis, while the accumulation of misfolded proteins within the ER lumen is believed to exert an osmotic force and draw water from the cytoplasm to distend the ER lumen. In this process, Ca2+ release from the ER also critically contributes to aggravating ER stress and ER dilation. This review focuses on the role of Ca2+ transport in paraptosis by summarizing the recent findings related to the actions of Ca2+-modulating paraptosis-inducing agents and discussing the potential cancer therapeutic strategies that may effectively induce paraptosis via Ca2+ signaling.

show abstract

Section: Paraptosis-inducing Agents Associated With Ca 2+ Imbalancementioning

confidence: 99%

Section: Lercanidipine + Proteasome Inhibitormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

Kim

Lee

Seo

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The 22-kDa isoform of Sorcin is upregulated at a high Ca 2þ concentration in ER to develop resistance to 5-FU, oxaliplatin, and irinotecan (85). In such a way, loperamide overcomes the resistance of bortezomib by enhancing the ER stress and ER dilation, which leads to the accumulation of misfolded proteins and disturbs the calcium homeostasis, which is conducive to subsequent paraptosis-like cell death in human colon cancer cells (86).…”

Section: Drug Resistancementioning

confidence: 99%

A Complex Role for Calcium Signaling in Colorectal Cancer Development and Progression

Wang

Huang

et al. 2019

Molecular Cancer Research

View full text Add to dashboard Cite

Clinical data suggest that many malignant cancers are associated with hypercalcemia. Hypercalcemia can facilitate the proliferation and metastasis of gastric and colon tumors, and has been considered a hallmark of end-stage disease. However, it has also been reported that dietary calcium or vitamin D supplementation could reduce the risk of many types of cancers. In particular, the intestines can absorb considerable amounts of calcium via Ca 2þ -permeable ion channels, and hypercalcemia is common in patients with colorectal cancer. Thus, this review considers the role of calcium signal-ing in the context of colorectal cancer and summarizes the functions of specific regulators of cellular calcium levels in the proliferation, invasion, metastasis, cell death, and drug resistance of colorectal cancer cells. The data reveal that even a slight upregulation of intracellular Ca 2þ signaling can facilitate the onset and progression of colorectal cancer, while continuous Ca 2þ influx and Ca 2þ overload may cause tumor cell death. This dual function of Ca 2þ signaling adds nuance to the debate over the hallmarks of colorectal cancer, and may even provide new directions and strategies for clinical interventions.

show abstract

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

Jiang

et al. 2022

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Loperamide overcomes the resistance of colon cancer cells to bortezomib by inducing CHOP-mediated paraptosis-like cell death

Cited by 22 publications

References 43 publications

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

A Complex Role for Calcium Signaling in Colorectal Cancer Development and Progression

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

Contact Info

Product

Resources

About