2-Bromopalmitate sensitizes osteosarcoma cells to adriamycin-induced apoptosis via the modulation of CHOP

Xu, Tong; Huang, Chao; Qi, Xiaotian; Yang, Xiaochun; Zhang, Ning; Cao, Ji; Wang, Chen; Zhu, Hong; Yang, Bo; He, Qiaojun; Shao, Xuejing

doi:10.1016/j.ejphar.2018.12.019

Cited by 14 publications

(8 citation statements)

References 42 publications

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“…Quantitative real-time RT-PCR analysis was performed by using TAKARA SYBR Premix EXTaq TM as previously described [24]. Reaction mixtures containing SYBR Green were prepared following the manufacturer's protocol.…”

Section: Reverse Transcription Pcrmentioning

confidence: 99%

Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells

et al. 2019

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Emerging evidence indicates that M2-polarized tumor-associated macrophages (TAMs) directly participate in tumor initiation, progression and metastasis. However, to date, few studies have investigated novel strategies for inhibiting TAMs in order to overcome osteosarcoma. In this study, we reported that M2 macrophages were enriched in osteosarcoma tissues from patients, and M2-polarized TAMs enhanced cancer initiation and stemness of osteosarcoma cells, thereby establishing M2-polarized TAMs as a therapeutic target for blocking osteosarcoma formation. We also found that all-trans retinoic acid (ATRA) weakened TAM-induced osteosarcoma tumor formation by inhibiting M2 polarization of TAMs in vivo, and inhibited the colony formation, as well as sphereformation capacity of osteosarcoma cells promoted by M2-type macrophages in vitro. Furthermore, M2-type macrophages enhanced cancer stem cells (CSCs) properties as assessed by increasing the numbers of CD117 + Stro-1 + cells accompanied by the upregulation of CSC markers (CD133, CXCR4, Nanog, and Oct4), which could clearly be reduced by ATRA. Taken together, the results of this study demonstrated the role of M2-polarized TAMs in osteosarcoma initiation and stemness by activating CSCs, and indicated that ATRA treatment is a promising approach for treating osteosarcoma by preventing M2 polarization of TAMs.

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Section: Reverse Transcription Pcrmentioning

confidence: 99%

Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells

et al. 2019

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“…As shown in Figure 3c, the expression of cyclinD and CDK2 was remarkably decreased, whereas the expression of p21 and Rb was increased in the combination group compared with the control group. In addition, previous studies reported a key role for ATM/Chks in DNA damagemediated cycle arrest (Lee & Paull, 2007;Xu et al, 2019). Following DNA damage, ATM and/or ATR are activated, resulting in the phosphorylation of Chks and p53.…”

Section: Zey Further Increases Cisplatin-mediated Cell Cycle Arrest I...mentioning

confidence: 95%

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Yang

Xiao

Sun

et al. 2021

Phytotherapy Research

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A safer and more effective combination strategy designed to enhance the efficacy and minimize the toxicity of cisplatin in osteosarcoma (OS) is urgently needed. Zeylenone (zey), a cyclohexene oxide compound, exerted an obvious inhibitory effect on several cancer cell lines and exhibited little cytotoxicity towards normal cells, enabling zey to play a unique role in combination therapy. Thus, the study aimed to determine whether the combination of zey and cisplatin produces synergistic antitumour effects on OS and to further explore molecular mechanisms. Initially, we found that zey potentiated the anti-osteosarcoma efficacy of cisplatin and exhibited synergistic interactions with cisplatin in vitro, which also were confirmed in vivo by using xenograft model. Mechanistically, zey and cisplatin synergistically induced DNA damage, cell cycle arrest, necrosis, and apoptosis in OS cells. Importantly, zey had a high binding affinity for Hsp90 and reduced the expression of Hsp90, which further induced the suppression of AKT/GSK3β signalling axis and the degradation of Fanconi anaemia (FA) pathway proteins. Thus, the Hsp90/AKT/GSK3β and FA pathway are the key to the synergism between zey and cisplatin. Overall, zey shows promise for development as a cisplatin chemosensitizer with clinical utility in restoring cisplatin sensitivity of cancer cells.

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“…Moreover, GNS561 and sorafenib (a multikinase inhibitor) were found to have a synergistic impact on preventing tumor development and cell proliferation in a mouse tumor model [ 142 , 143 ] (Table 1 ). In addition, the combination of adriamycin (an antibiotic drug) and 2‐BP strongly inhibited the proliferation of osteosarcoma cell lines and primary osteosarcoma cells [ 144 ] (Table 1 ).…”

Section: Targeting Protein Palmitoylation In Cancermentioning

confidence: 99%

Protein palmitoylation in cancer: molecular functions and therapeutic potential

et al. 2022

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Protein S‐palmitoylation (hereinafter referred to as protein palmitoylation) is a reversible lipid posttranslational modification catalyzed by the zinc finger DHHC‐type containing (ZDHHC) protein family. The reverse reaction, depalmitoylation, is catalyzed by palmitoyl‐protein thioesterases (PPTs), including acyl‐protein thioesterases (APT1/2), palmitoyl protein thioesterases (PPT1/2), or alpha/beta hydrolase domain‐containing protein 17A/B/C (ABHD17A/B/C). Proteins encoded by several oncogenes and tumor suppressors are modified by palmitoylation, which enhances the hydrophobicity of specific protein subdomains, and can confer changes in protein stability, membrane localization, protein–protein interaction, and signal transduction. The importance for protein palmitoylation in tumorigenesis has just started to be elucidated in the past decade; palmitoylation appears to affect key aspects of cancer, including cancer cell proliferation and survival, cell invasion and metastasis, and antitumor immunity. Here we review the current literature on protein palmitoylation in the various cancer types, and discuss the potential of targeting of palmitoylation enzymes or palmitoylated proteins for tumor treatment.

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2-Bromopalmitate sensitizes osteosarcoma cells to adriamycin-induced apoptosis via the modulation of CHOP

Cited by 14 publications

References 42 publications

Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells

Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells

Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Protein palmitoylation in cancer: molecular functions and therapeutic potential

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