JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin

Abstract

-Recent evidence shows that tumor microenvironment containing heterogeneous cells may be involved in cancer initiation, growth and tumor cell response to anticancer therapy. Chemotherapy was designed to make toxic impact on malicious cells in organisms, however, the means to protect healthy cells against chemical toxicity are still unsuccessful. As known, the majority of tumor surrounding cells are cancer-associated adipocytes which influence cancer development, progression and treatment. Targeting the components of tumor microenvironment in combination with conventional cancer treatment may become an effective cancer therapy strategy. However, little is known about adipocyte death mechanisms during combined chemo-and targeted therapy. The importance of c-Jun-NH 2 -terminal kinase (JNK) signaling in tumor development and treatment has been demonstrated using various in vitro and in vivo cancer models. The aim of this study was to ascertain adipocyte viability during simultaneous stress kinase JNK inhibition and exposure to one of the most commonly used anticancer drugs cis-diamminedichloroplatinum II (cisplatin). Our model involved adipocyte-like cells (ADC) which were obtained during in vitro differentiation of adult rabbit muscle-derived stem cells. Cisplatin induced apoptotic cell death. During 24-hr cisplatin treatment gradual, strong and prolonged increase of both JNK and its target protein c-Jun phosphorylation was found in ADC. Pre-treatment of cells with SP600125 decreased cisplatin-induced activation of c-Jun and promoted apoptosis. Upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-2 proteins were found to be regulated in JNK-dependent manner. Thus, the results prove the antiapoptotic role of activated JNK in adipocyte-like cells treated with cisplatin.

RETRACTED ARTICLE: Alginate oligosaccharide attenuates α2,6-sialylation modification to inhibit prostate cancer cell growth via the Hippo/YAP pathway

“…Various types of stimulation such as drugs and ultraviolet irradiation can induce c-Jun activation 43 . Activated c-Jun participates in various physiological processes such as proliferation and apoptosis of tumor cells by regulating target gene transcription 44 . A previous study showed that the interaction between KLF5 and c-Jun promoted Angiotensin II-induced suppression of p21 expression in vascular smooth muscle cells 45 .…”

Expressions and Regulatory Effects of P38/ERK/JNK Mapks in the Adipogenic Trans-Differentiation of C2C12 Myoblasts

“…We noted that cells were reduced after SP600125 treatment at later stages of trans-differentiation, and studies suggest that MAPKs participate in apoptosis [23, 24]. Data for all treatment groups show that (Fig.…”

An inhibitor of the acetyltransferases CBP/p300 exerts antineoplastic effects on gastrointestinal stromal tumor cells

“…Therefore, CBP is required for tumor growth through ERK1/2 phosphorylation and apoptosis regulation via inactivation of JNK in GIST882 cells, whereas p300 does not appear to contribute to these activities. However, both CBP and p300 silencing led to the upregulation of proapoptotic Bax and the downregulation of anti-apoptotic Bcl-2 and Bcl-xL, members of the Bcl-2 family that are involved in the mitochondrial cell death pathway (41), suggesting that CBP/p300 affect apoptosis through the regulation of Bcl-2 family proteins. Thus, CBP may regulate apoptosis via both the death receptor signaling pathway and the mitochondrial cell death pathway in GIST cells.…”