Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines

Asbagh, Layka Abbasi; Uzunoğlu, Selim; Çal, Çağ

doi:10.1590/s1677-55382008000300013

Cited by 8 publications

(6 citation statements)

References 30 publications

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“…For example, luteolin, a flavonoid, reduced LPS-induced IL-6 production by inhibiting the Jun N-terminal kinase (JNK)-activator protein 1 pathway,26 while chloroquine-mediated inhibition of IL-6 expression was associated with reduced mRNA stability and mRNA levels 27. In addition, the bisphosphonate zoledronic acid was also reported to downregulate IL-6 gene expression in prostate cancer cells though the underlying mechanism is unclear 28. In contrast, many therapeutic agents are associated with the upregulation of IL-6 expression, including paclitaxel through the activation of the JNK and Toll-like receptor 4 signaling pathways29 and the multi-kinase inhibitor sunitinib through a yet-to-be-identified mechanism 30.…”

Section: Discussionmentioning

confidence: 99%

“…27 In addition, the bisphosphonate zoledronic acid was also reported to downregulate IL-6 gene expression in prostate cancer cells although the underlying mechanism is unclear. 28 In contrast, many therapeutic agents are associated with the upregulation of IL-6 expression, including paclitaxel through the activation of the JNK and Toll-like receptor 4 signaling pathways 29 and the multikinase inhibitor sunitinib through a yet-to-be-identified mechanism. 30 Consequently, understanding the mechanism of this AMPK-independent induction will shed light onto the regulation of IL-6 production.…”

Section: Discussionmentioning

confidence: 99%

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Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators

et al. 2010

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In light of the unique ability of thiazolidinediones to mediate peroxisome proliferator-activated receptor (PPAR)γ-independent activation of adenosine monophosphate-activated protein kinase (AMPK) and suppression of interleukin (IL)-6 production, we conducted a screening of an in-house, thiazolidinedione-based focused compound library to identify novel agents with these dual pharmacological activities. Cell-based assays pertinent to the activation status of AMPK and mammalian homolog of target of rapamycin (i.e., phosphorylation of AMPK and p70 ribosomal protein S6 kinase, respectively), and IL-6/IL-6 receptor signaling (i.e., IL-6 production and signal transducer and activator of transcription 3 phosphorylation, respectively) in lipopolysaccharide (LPS)-stimulated THP-1 human macrophages were used to screen this compound library, which led to the identification of compound 53 (N-{4-[3-(1-Methylcyclohexylmethyl)-2,4-dioxothiazolidin-5-ylidene-methyl]-phenyl}-4-nitro-3-trifluoromethyl-benzenesulfonamide) as the lead agent. Evidence indicates that this drug-induced suppression of LPS-stimulated IL-6 production was attributable to AMPK activation. Furthermore, compound 53-mediated AMPK activation was demonstrated in C-26 colon adenocarcinoma cells, indicating that it is not a cell line-specific event.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators

et al. 2010

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“…However, PC-3 cells produced the high level of IL-6 in our ELISA assay (Figure 3a) and in other previous reports. 32,33 IL-6 may stimulate PC-3 cell growth through other signaling pathways such as the extracellular signal-regulated kinase 1 and 2 (ERK1/2)-mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase (PI3-K) pathway. 26 In the ELISA assay, both human CRPC cell lines, DU-145 and PC-3, produced a high level of IL-6 protein, but the TRAMP-C2 mouse CRPC cell line did not produce a substantial level of IL-6 protein (Figure 3a).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration-resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo

et al. 2019

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“…Zoledronic acid (ZA) is the most potent nitrogen-containing bisphosphonate compound which has been used in adjuvant therapies to inhibit bone metastasis caused by multiple cancers [172]. It inhibits growth, besides inducing apoptosis by reducing IL-6 secretion in prostate cancer cell lines, which is suggestive of its use in the treatment of prostate cancer either alone or in combination with chemotherapy [171]. Radiation activates IL-6/STAT-3 signalling, which stimulates tumour invasion and EMT changes and promotes the survival of tumour cells after therapy, thereby conferring resistance to therapy [12,84,156].…”

Section: Il-6 Induces Therapeutic Resistance In Cancermentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

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In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.

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Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines

Cited by 8 publications

References 30 publications

Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators

Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators

Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration-resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo

Role of interleukin-6 in cancer progression and therapeutic resistance

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