Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt’s Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70

Xu, Naijin; Chen, Yu; Liu, Wei 'e; Chen, Yanjie; Fan, Zhimin; Liu, Min; Li, Lin-Jie

doi:10.12659/msm.910170

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…On the other hand, HSP70 regulates the cellular redox status. Blocking the JAK2/STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) signaling pathway promotes OS and cell apoptosis via the downregulation of HSP70 [ 56 ]. HSP27 has many additional functions.…”

Section: Heat Shock Proteins and Oxidative Stressmentioning

confidence: 99%

Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Szyller

Bil‐Lula

2021

Oxidative Medicine and Cellular Longevity

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Heat shock proteins (HSPs) are molecular chaperones produced in response to oxidative stress (OS). These proteins are involved in the folding of newly synthesized proteins and refolding of damaged or misfolded proteins. Recent studies have been focused on the regulatory role of HSPs in OS and ischemia/reperfusion injury (I/R) where reactive oxygen species (ROS) play a major role. ROS perform many functions, including cell signaling. Unfortunately, they are also the cause of pathological processes leading to various diseases. Biological pathways such as p38 MAPK, HSP70 and Akt/GSK-3β/eNOS, HSP70, JAK2/STAT3 or PI3K/Akt/HSP70, and HSF1/Nrf2-Keap1 are considered in the relationship between HSP and OS. New pathophysiological mechanisms involving ROS are being discovered and described the protein network of HSP interactions. Understanding of the mechanisms involved, e.g., in I/R, is important to the development of treatment methods. HSPs are multifunctional proteins because they closely interact with the antioxidant and the nitric oxide generation systems, such as HSP70/HSP90/NOS. A deficiency or excess of antioxidants modulates the activation of HSF and subsequent HSP biosynthesis. It is well known that HSPs are involved in the regulation of several redox processes and play an important role in protein-protein interactions. The latest research focuses on determining the role of HSPs in OS, their antioxidant activity, and the possibility of using HSPs in the treatment of I/R consequences. Physical exercises are important in patients with cardiovascular diseases, as they affect the expression of HSPs and the development of OS.

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Section: Heat Shock Proteins and Oxidative Stressmentioning

confidence: 99%

Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Szyller

Bil‐Lula

2021

Oxidative Medicine and Cellular Longevity

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“…30 Jing et al 31 apoptosis by downregulating the anti-apoptotic proteins. 34 Cyanidin-3-glucoside, a structurally similar to delphinidin directly represses STAT-3 expression in breast cancer cells. 35 Moreover, delphinidin potentially inhibited STAT-3 activation via modulation of Met receptor phosphorylation in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Delphinidin modulates JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells

Zhang

Pan

Zhao

et al. 2021

Environmental Toxicology

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Delphinidin is an anthocyanin that belongs to the group of flavonoids that exert numerous biological activities. However, the molecular mechanisms underlying the anticancer effects of delphinidin remain poorly understood. In our study we analyzed delphinidin modulate STAT-3 and MAPKinase signaling thereby inhbits cell proliferation and promote apoptosis. Our study demonstrated that delphinidin treatment significantly reduced the viability of human colon cancer HCT116 in a concentrationdependent manner. We noticed that delphinidin effectively induced oxidative stressmediated apoptosis by generating intracellular ROS, decreasing antioxidant levels, inducing lipid peroxidation, and single-strand break on colon cancer cells. In this study, we observed that delphinidin treatment alters the mitochondrial membrane potential, thereby induces apoptosis was closely associated with the induction of pro-apoptotic Bax, Caspase-3,8 & 9, cytochrome C, and inhibition of anti-apoptotic protein expression. Studies on STAT-3 and MAPKinase signaling showed delphinidin inhibited the phosphorylation of these transcription factors' activity. Inhibition of STAT-3, p38, and ERK1/2 phosphorylation and modulation pro-apoptotic protein expression might be responsible for the anticancer activity of delphinidin in colon cancer cells.

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“…When the STAT signaling pathway is constitutively active in tumors, like in breast and colon cancer, STAT3 has also been shown to transcriptionally induce HSP27 expression [194]. Though less documented, this mechanism also exists in hematological malignancies like Burkitt's lymphoma, where pharmacological inhibition of STAT3 by AG490 downregulates HSP70 expression [195].…”

Section: Hsf/hsps and Jak/statmentioning

confidence: 99%

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Hermetet

Girodon

Jego

2019

Cancers

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While cells from multicellular organisms are dependent upon exogenous signals for their survival, growth, and proliferation, commitment to a specific cell fate requires the correct folding and maturation of proteins, as well as the degradation of misfolded or aggregated proteins within the cell. This general control of protein quality involves the expression and the activity of molecular chaperones such as heat shock proteins (HSPs). HSPs, through their interaction with the STAT3/STAT5 transcription factor pathway, can be crucial both for the tumorigenic properties of cancer cells (cell proliferation, survival) and for the microenvironmental immune cell compartment (differentiation, activation, cytokine secretion) that contributes to immunosuppression, which, in turn, potentially promotes tumor progression. Understanding the contribution of chaperones such as HSP27, HSP70, HSP90, and HSP110 to the STAT3/5 signaling pathway has raised the possibility of targeting such HSPs to specifically restrain STAT3/5 oncogenic functions. In this review, we present how HSPs control STAT3 and STAT5 activation, and vice versa, how the STAT signaling pathways modulate HSP expression. We also discuss whether targeting HSPs is a valid therapeutic option and which HSP would be the best candidate for such a strategy.

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Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt’s Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70

Cited by 16 publications

References 39 publications

Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Delphinidin modulates JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

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