Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway.

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway. J Cell Mol Med. 2018 Jul 11;: Authors: Jin W, Zhou L, Yan B, Yan L, Liu F, Tong P, Yu W, Dong X, Xie L, Zhang J, Xu Y, Li C, Yuan Q, Shan L, Efferth T Abstract Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti-cancer activity. To evaluate its anti-osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy. The cellular data confirmed that TB-triggered DNA damage and induced apoptosis of U2OS cells by regulation of Mki67, PARP, caspase 3 and H2AX, and Western blot assay showed an activation of p53 signalling pathway. When P53 was knocked down by siRNA, the subsequent downstream signalling was blocked, indicating a p53-dependent mechanism of TB on U2OS cells (p53 wt). Using osteosarcoma cell lines with p53 mutations (HOS, SAOS-2 and MG63), we found that TB exerted stronger inhibitory effect on U2OS cells than that on p53-mut cell lines, but it also exerted obviou...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research

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Abstract BACKGROUND: Transforming acidic coiled-coil containing protein 3 (TACC3) is expressed during the mitotic phase of nuclear division and regulates microtubules. Recently, high TACC3 expression in tumor cells of various cancers including soft tissue sarcoma has been reported. However, its role in osteosarcoma remains unknown. Because we have few prognostic markers for survival in osteosarcoma, we wanted to investigate the potential role of TACC3 in human osteosarcoma and determine if it is associated with survival. QUESTIONS/PURPOSES: (1) Is there a relationship between TACC3 expression and clinicopatho...
Source: Clinical Orthopaedics and Related Research - Category: Orthopaedics Authors: Tags: Clin Orthop Relat Res Source Type: research
ConclusionsThe results of this study highlight the crucial role of GPR137 in promoting osteosarcoma cell growth in vitro. GPR137 could serve as a potential therapeutic target against osteosarcoma.
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsTaken together, these data demonstrate that brazilin induces osteosarcoma cell death by inducing excessive autophagy, which is mediated through the Ca2+-FOXO3A pathway. Our study provides a new anti-tumour mechanism for brazilin treatment in osteosarcoma patients.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionsThe results of this study highlight the crucial role of GPR137 in promoting osteosarcoma cell growth in vitro. GPR137 could serve as a potential therapeutic target against osteosarcoma.
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research
Abstract In the past decades, chemotherapy has resulted in improved outcomes for patients with osteosarcoma. However, resistance to chemotherapy often leads to poor prognoses. Cisplatin is a standard drug for osteosarcoma therapy, and chemoresistance to cisplatin in osteosarcoma limits the effectiveness of chemotherapy drugs. Transglutaminase 2 (TGM2) is a member of the transglutaminase family, and it is reported to be associated with chemoresistance in various types of cancer. The present study aimed to investigate the function of TGM2 in regulating chemosensitivity of osteosarcoma cells to cisplatin. For in...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
In this study, we showed that the expression level of Kruppel-like factor 4 (KLF4) is highly associated with human osteosarcoma cancer stemness. KLF4-overexpressed osteosarcoma cells displayed characteristics of OSCs: increased sphere-forming potential, enhanced levels of stemness-associated genes, great chemoresistance to adriamycin and CDDP, as well as more metastasis potential. Inversely, KLF4 knockdown could reduce colony formation in vitro and inhibit tumorigenesis in vivo, supporting an oncogenic role for KLF4 in osteosarcoma pathogenesis. Furthermore, KLF4 was shown to activate the p38 MAPK signaling pathway to prom...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
In this study, we investigated the vital function of MALAT1 in the progression of OS and its potential leading mechanism, altering the expression and localization of β-catenin via epigenetic transcriptional regulation by interacting with EZH2. With the help of MALAT1 silencing using small interfering RNAs (siRNAs), the loss of E-cadherin of MNNG/HOS cells was rescued, and the abnormal expression and localization of β-catenin were corrected at the same time. Overall, our research showed promising potential for new treatment strategies based on epigenetic regulation targeting MALAT1, which will not only coordinate ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood.
Source: Cancer Letters - Category: Cancer & Oncology Authors: Tags: Original Articles Source Type: research
Histone methyltransferase SETD2 regulates osteosarcoma cell growth and chemosensitivity by suppressing Wnt/β-catenin signaling. Biochem Biophys Res Commun. 2018 May 29;: Authors: Jiang C, He C, Wu Z, Li F, Xiao J Abstract SETD2 is a histone methyltransferase that catalyzes the trimethylation of lysine 36 on histone 3. SETD2 is frequently found to be mutated or deleted in a variety of human tumors, whereas the role of SETD2 in oncogenesis of osteosarcoma has never been defined. Here in our study, we uncovered that SETD2 regulates tumor growth and chemosensitivity of osteosarcoma. Overexpression of...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
ConclusionsCmax did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however,Cmax correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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