Inhibition of PKCα reduces the ability of migration of kidney cancer cells but has no impact on cell apoptosis

Zhan, Bo; Kong, Chuize; Zhang, Zhe; Dong, Xiao; Zhang, Naiwen

doi:10.3892/etm.2017.4258

Cited by 5 publications

(4 citation statements)

References 23 publications

(22 reference statements)

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“…PKCα is involved in the proliferation, migration, invasion, and apoptosis, signal transducers and activators of PKCα are constitutively activated in many human solid tumors including breast cancer, and inhibition of PKCα was consider as a novel strategy in developing anticancer agents development, cellular proliferation, and migration . In the present study, we demonstrated the ability of miR‐216a to activate apoptosis through the regulation of PKCα in breast cancer cells.…”

Section: Discussionsupporting

confidence: 49%

miR‐216a promotes breast cancer cell apoptosis by targeting PKCα

Cui

Wang

Liu

et al. 2019

Fundamemntal Clinical Pharma

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Breast cancer (BC) is the most common cause of death in women throughout the world. MicroRNAs (miRNAs, miR) have been identified as key regulators in carcinogenesis of several cancers, including BC. MicroRNA‐216a (miR‐216a) is downregulated in several cancers. Here, we evaluated the effects of miRNA‐216a on breast cancer cells and the underlying mechanisms. miR‐216a level was quantified by real‐time RT‐PCR. Cell viability was analyzed by MTT assay. Wound‐healing assay was performed for detection of cell migration. Apoptosis was detected by TUNEL and caspase‐3 activity assay. Moreover, the level of protein expression was determined by Western blot. We found that miR‐216a expression was remarkably decreased in both human BC tissues and MCF‐7 cells. miR‐216a overexpression dramatically suppressed the migration and promoted the apoptosis in cultured MCF‐7 cells. We validated PKCα (protein kinase C alpha, PRKCA) as a direct target of miR‐216a. Knockdown of PKCα induced apoptosis and inhibited migration in cultured MCF‐7 cells which were reversed by miR‐216a inhibitor. Moreover, the level of miR‐216a is negatively correlated with PKCα in cell lines. Our results collectively suggest that miR‐216a suppressed migration and promoted apoptosis in breast cancer cells by targeting PKCα. These findings indicate that manipulation of miR‐216a expression may represent a novel therapeutic strategy in the treatment of breast cancer.

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Section: Discussionsupporting

confidence: 49%

miR‐216a promotes breast cancer cell apoptosis by targeting PKCα

Cui

Wang

Liu

et al. 2019

Fundamemntal Clinical Pharma

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“…While Harazono and colleagues demonstrated that MCP suppressed Gal:Bax heterodimerization and promoted apoptosis 63, Li and co-workers showed that MCP attenuated CDDP-induced AKI by suppressing protein kinase C-α (PKC-α)-driven apoptosis 25. These opposite findings may be explained by the fact that MCP, in similar manner as PKC-α, interferes with multiple intracellular pathways and, therefore, could acts as pro- or anti-apoptotic agent, depending upon cell type or tissue microenvironment 65-68. Furthermore, different effects of Gal-3 inhibition in modulation of CDDP-induced apoptosis could be due to the different doses of CDDP (16mg/kg vs. 20mgkg body weight) which were used in our and in study conducted by Li and colleagues 25.…”

Section: Discussionmentioning

confidence: 99%

Galectin 3 protects from cisplatin-induced acute kidney injury by promoting TLR-2-dependent activation of IDO1/Kynurenine pathway in renal DCs

et al. 2019

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Strategies targeting cross-talk between immunosuppressive renal dendritic cells (DCs) and T regulatory cells (Tregs) may be effective in treating cisplatin (CDDP)-induced acute kidney injury (AKI). Galectin 3 (Gal-3), expressed on renal DCs, is known as a crucial regulator of immune response in the kidneys. In this study, we investigated the role of Gal-3 for DCs-mediated expansion of Tregs in the attenuation of CDDP-induced AKI.Methods: AKI was induced in CDDP-treated wild type (WT) C57BL/6 and Gal-3 deficient (Gal-3-/-) mice. Biochemical, histological analysis, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, real-time PCR, magnetic cell sorting, flow cytometry and intracellular staining of renal-infiltrated immune cells were used to determine the differences between CDDP-treated WT and Gal-3-/- mice. Newly synthesized selective inhibitor of Gal-3 (Davanat) was used for pharmacological inhibition of Gal-3. Recombinant Gal-3 was used to demonstrate the effects of exogenously administered soluble Gal-3 on AKI progression. Pam3CSK4 was used for activation of Toll-like receptor (TLR)-2 in DCs. Cyclophosphamide or anti-CD25 antibody were used for the depletion of Tregs. 1-Methyl Tryptophan (1-MT) was used for pharmacological inhibition of Indoleamine 2,3-dioxygenase-1 (IDO1) in TLR-2-primed DCs which were afterwards used in passive transfer experiments.Results: CDDP-induced nephrotoxicity was significantly more aggravated in Gal-3-/- mice. Significantly reduced number of immunosuppressive TLR-2 and IDO1-expressing renal DCs, lower serum levels of KYN, decreased presence of IL-10-producing Tregs and significantly higher number of inflammatory IFN-γ and IL-17-producing neutrophils, Th1 and Th17 cells were observed in the CDDP-injured kidneys of Gal-3-/- mice. Pharmacological inhibitor of Gal-3 aggravated CDDP-induced AKI in WT animals while recombinant Gal-3 attenuated renal injury and inflammation in CDDP-treated Gal-3-/- mice. CDDP-induced apoptosis, driven by Bax and caspase-3, was aggravated in Gal-3-/- animals and in WT mice that received Gal-3 inhibitor (CDDP+Davanat-treated mice). Recombinant Gal-3 managed to completely attenuate CDDP-induced apoptosis in CDDP-injured kidneys of Gal-3-/- mice. Genetic deletion as well as pharmacological inhibition of Gal-3 in renal DCs remarkably reduced TLR-2-dependent activation of IDO1/KYN pathway in these cells diminishing their capacity to prevent transdifferentiation of Tregs in inflammatory Th1 and Th17 cells. Additionally, Tregs generated by Gal-3 deficient DCs were not able to suppress production of IFN-γ and IL-17 in activated neutrophils. TLR-2-primed DCs significantly enhanced capacity of Tregs for attenuation of CDDP-induced AKI and inflammation and expression of Gal-3 on TLR-2-primed DCs was crucially important for their capacity to enhance nephroprotective and immunosuppressive properties of Tregs. Adoptive transfer of TLR-2-primed WTDCs significantly expanded Tregs in the kidneys of CDDP-treated WT and Gal-3-/- recipients resulting in the suppress...

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“…Irradiation initiates c-Abl/PKCδ/Rac1/p38 cascades and leads to the oligomerization of Bax and Bak, which results in the release of cytochrome C [ 48 ]. It has been demonstrated that PKCα might not contribute to the progression of kidney carcinoma since its inhibition does not affect kidney cancer cell apoptosis [ 49 ]. Additionally, in some reports, PKC activation by oxidative stress and irradiation is not always accompanied by translocation [ 50 ].…”

Section: Pkcs In Cancermentioning

confidence: 99%

Targeting Protein Kinase C for Cancer Therapy

Huang

et al. 2022

Cancers

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Protein kinase C (PKC) isoforms, a group of serine-threonine kinases, are important regulators in carcinogenesis. Numerous studies have demonstrated that PKC isoforms exert both positive and negative effects on cancer cell demise. In this review, we systematically summarize the current findings on the architecture, activity regulation and biological functions of PKCs, especially their relationship with anti-cancer therapy-induced cell death. Additionally, we elaborate on current knowledge of the effects of PKCs on tumor metabolism and microenvironment, which have gained increasing attention in oncology-related areas. Furthermore, we underscore the basic experimental and clinical implications of PKCs as a target for cancer therapy to evaluate their therapeutic benefits and potential applications.

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Inhibition of PKCα reduces the ability of migration of kidney cancer cells but has no impact on cell apoptosis

Cited by 5 publications

References 23 publications

miR‐216a promotes breast cancer cell apoptosis by targeting PKCα

miR‐216a promotes breast cancer cell apoptosis by targeting PKCα

Galectin 3 protects from cisplatin-induced acute kidney injury by promoting TLR-2-dependent activation of IDO1/Kynurenine pathway in renal DCs

Targeting Protein Kinase C for Cancer Therapy

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