Quercetin Attenuates Copper-Induced Apoptotic Cell Death and Endoplasmic Reticulum Stress in SH-SY5Y Cells by Autophagic Modulation

Chakraborty, Joyeeta; Pakrashi, Sourav; Sarbajna, Arpita; Dutta, Moumita; Bandyopadhyay, Jaya

doi:10.1007/s12011-022-03093-x

Cited by 26 publications

(13 citation statements)

References 56 publications

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“…Furthermore, it was found that quercetin supplementation could decrease the ratio of Bax/Bcl-2, the release of CytC, and the activation of caspases-9 and -3, and an increase in cleaved-PARP1 caused by QCT exposure in L02 cells ( Figure 6 and Figure 7 ). Several studies have shown that quercetin supplementation could improve diabetes-induced testicular anomaly [ 58 ], and d-galactosamine-induced human L02 cell damage [ 59 ], and copper-induced apoptotic cell death [ 60 ] by inhibiting the oxidative-stress-driven mitochondrial apoptotic pathway. Taken together, this evidence indicated that quercetin could offer a protective effect against QCT-induced apoptosis by inhibiting mitochondrial pathways, which may be related to the inhibitory effect on the production of ROS.…”

Section: Discussionmentioning

confidence: 99%

Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway

et al. 2022

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Quinocetone (QCT), a member of the quinoxaline 1,4-di-N-oxides (QdNOs) family, can cause genotoxicity and hepatotoxicity, however, the precise molecular mechanisms of QCT are unclear. This present study investigated the protective effect of quercetin on QCT-induced cytotoxicity and the underlying molecular mechanisms in human L02 and HepG2 cells. The results showed that quercetin treatment (at 7.5–30 μM) significantly improved QCT-induced cytotoxicity and oxidative damage in human L02 and HepG2 cells. Meanwhile, quercetin treatment at 30 μM significantly inhibited QCT-induced loss of mitochondrial membrane potential, an increase in the expression of the CytC protein and the Bax/Bcl-2 ratio, and an increase in caspases-9 and -3 activity, and finally improved cell apoptosis. Quercetin pretreatment promoted the expression of the phosphorylation of p38, Nrf2, and HO-1 proteins. Pharmacological inhibition of p38 significantly inhibited quercetin-mediated activation of the Nrf2/HO-1 pathway. Consistently, pharmacological inhibitions of the Nrf2 or p38 pathways both promoted QCT-induced cytotoxicity and partly abolished the protective effects of quercetin. In conclusion, for the first time, our results reveal that quercetin could improve QCT-induced cytotoxicity and apoptosis by activating the p38/Nrf2/HO-1 pathway and inhibiting the ROS/mitochondrial apoptotic pathway. Our study highlights that quercetin may be a promising candidate for preventing QdNOs-induced cytotoxicity in humans or animals.

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Section: Discussionmentioning

confidence: 99%

Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway

et al. 2022

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“…In SH-SY5Y cells, quercetin also induced autophagy by upregulating LC3II. This study also revealed that quercetin restored organelle endoplasmic reticulum homeostasis and alleviated the cytotoxic damage induced to Cu by regulating the autophagic pathway ( Chakraborty et al, 2022 ). Moreover, the highest number of cellular autophagic vacuoles was observed in HeLa cells treated with 50 μM quercetin, but the number decreased instead at higher doses ( Wang et al, 2016 ).…”

Section: Therapeutic Mechanisms Of Quercetin Targeting Non-apoptotic ...mentioning

confidence: 85%

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy

Yang

Xu²,

Tang³

et al. 2022

Front. Pharmacol.

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The ultimate goal of cancer treatment is to kill cancer cells, based on the use of various therapeutic agents, such as chemotherapy, radiotherapy, or targeted therapy drugs. Most drugs exert their therapeutic effects on cancer by targeting apoptosis. However, alterations in apoptosis-related molecules and thus assisting cells to evade death, eventually lead to tumor cell resistance to therapeutic drugs. The increased incidence of non-apoptotic cell death modes such as induced autophagy, mitotic catastrophe, senescence, and necrosis is beneficial to overcoming multidrug resistance mediated by apoptosis resistance in tumor cells. Therefore, investigating the function and mechanism of drug-induced non-apoptotic cell death modes has positive implications for the development of new anti-cancer drugs and therapeutic strategies. Phytochemicals show strong potential as an alternative or complementary medicine for alleviating various types of cancer. Quercetin is a flavonoid compound widely found in the daily diet that demonstrates a significant role in inhibiting numerous human cancers. In addition to direct pro-tumor cell apoptosis, both in vivo and in vitro experiments have shown that quercetin exerts anti-tumor properties by triggering diverse non-apoptotic cell death modes. This review summarized the current status of research on the molecular mechanisms and targets through which quercetin-mediated non-apoptotic mode of cancer cell death, including autophagic cell death, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc.

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“…Here, we will briefly discuss the relationship between mitochondria and cancer from the perspective of the mitochondrial membrane. It has been found that the collapse of mitochondrial membrane potential induced apoptosis in cancer cells 98,99 . Furthermore, exogenous lipids can regulate the mitochondrial membrane function, such as changing membrane permeability and affecting membrane potential 100 .…”

Section: Compositional Changes Of Fa In Membrane Structures Of Cancer...mentioning

confidence: 99%

“…It has been found that the collapse of mitochondrial membrane potential induced apoptosis in cancer cells. 98,99 Furthermore, exogenous lipids can regulate the mitochondrial membrane function, such as changing membrane permeability and affecting membrane potential. 100 For example, a large number of studies related to colon cancer have demonstrated that n-3 PUFA can effectively reduce tumorigenesis by enhancing the unsaturation of mitochondrial PLs.…”

Section: Effects Of the Compositional Changes Of Fa On Mitochondrial ...mentioning

confidence: 99%

Fatty acids in cancer: Metabolic functions and potential treatment

Wang

Huang

et al. 2023

MedComm – Oncology

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Lipid metabolic reprogramming is one of the important metabolic characteristics of cancer cells. As major components of lipids, fatty acids provide energy and material basis for cancer cell survival. Abnormal fatty acid metabolism has been found in many cancers. Fatty acid uptake, transport, and synthesis are closely related to the pathogenesis of cancer. Meanwhile, fatty acid changes in the membrane structure of cancer cells and signal transduction mediated by signaling lipids are also helping cancer cells survive in the changing microenvironment. Some of these enzymes and metabolites involved in fatty acid metabolism are emerging as unique cancer biomarkers. Multiple studies have shown that disordered fatty acids can regulate tumor cell proliferation, metastasis, and drug resistance. Therefore, targeting fatty acid metabolism has become a promising treatment strategy. Here, we mainly present metabolic alterations of fatty acids, the basic components of lipids, in cancer. We discuss the cancer treatment based on fatty acid and fatty acid metabolism. These may provide a basis for a better understanding of lipid metabolic reprogramming in cancer, and also provide new ideas for cancer biomarker search, drug development, and combination therapy.

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Quercetin Attenuates Copper-Induced Apoptotic Cell Death and Endoplasmic Reticulum Stress in SH-SY5Y Cells by Autophagic Modulation

Cited by 26 publications

References 56 publications

Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway

Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy

Fatty acids in cancer: Metabolic functions and potential treatment

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