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Jun Bai, Bin-Jian Yang, Xin Luo
5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG), a novel synthetic isoflavone derivative, was demonstrated to possess antitumor activity in gastric cancer and breast cancer in vitro , but its antitumor effect and mechanism in ovarian cancer has not been characterized. The aim of the present study was to investigate the effects of HNPG on inhibiting the proliferation and invasion in human ovarian cancer A2780 cell lines of cisplatin resistance (A2780/DDP) and elucidate its underlying molecular mechanism. The results indicated that HNPG presented with marked antitumor activity against A2780/DDP cells in vitro , significantly inhibited the rates of proliferation, clone formation, invasion and metastasis, and markedly induced apoptosis in dose- and time-dependent manner...
April 2018: Oncology Letters
Jikui Xiong, Yan Wang, Yanli Gu, Yadong Xue, Lin Dang, Yuzhen Li
Malignant melanoma is characterized by rapid deterioration, early metastasis and high mortality. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1), which catalyzes 2-methylthio (ms2 ) modification of mitochondrial transfer RNAs, has been reported to induce cancer cell apoptosis, by a phospho-c-Jun N-terminal kinase (p-JNK) signaling pathway. The present study was the first to report on the association between CDK5RAP1 deficiency and nuclear factor-κB (NF-κB) signaling pathway during the apoptosis process in human malignant melanoma (A375) cells...
April 2018: Oncology Letters
Xuejiao Song, Tiantao Gao, Qian Lei, Lidan Zhang, Yuqin Yao, Jingyuan Xiong
Malignant melanoma is a devastating skin cancer due to its severe drug resistance and prompt metastasis. Piperlongumine is an anti-inflammation and tumor-suppressing natural product with defined structure. While numerous studies revealed exceptional inhibitory effects of piperlongumine on several carcinomas, few investigations were performed on melanoma. Therefore, the present study investigated the anti-tumor effects of piperlongumine on human melanoma cells in vitro, and explored the mechanisms of action...
March 15, 2018: Nutrition and Cancer
Xiaoye Yang, Xiaoqun Shi, Jianbo Ji, Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs)...
November 2018: Drug Delivery
Hao Zhuang, Qiang Li, Xinran Zhang, Xuda Ma, Zun Wang, Yun Liu, Xianfu Yi, Ruibing Chen, Feng Han, Ning Zhang, Yongmei Li
Metabolic reprogramming is a hallmark of cancer. Glycine decarboxylase (GLDC), an oxidoreductase, plays an important role in amino acid metabolism. While GLDC promotes tumor initiation and proliferation in non-small cell lung cancer and glioma and it was reported as a putative tumor suppressor gene in gastric cancer, the role of GLDC in hepatocellular carcinoma (HCC) is unknown. In the current study, microarray-based analysis suggested that GLDC expression was low in highly malignant HCC cell lines, and clinicopathological analysis revealed a decrease in GLDC in HCC tumor samples...
March 7, 2018: Free Radical Biology & Medicine
Wei Li, Zhengdong Jiang, Xue Xiao, Zheng Wang, Zheng Wu, Qingyong Ma, Lei Cao
Curcumin is a natural polyphenol compound derived from turmeric. It possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and anti-tumor progression properties. Our recent study demonstrated that superoxide dismutase (SOD)-dependent production of hydrogen peroxide (H2O2) promoted the invasive and migratory activity of pancreatic cancer cells. However, whether curcumin suppresses SOD-induced cancer progression and the related mechanisms remains unclear. Since epithelial‑to-mesenchymal transition (EMT) plays a key role in tumor metastasis, the aim of the present study was to examine whether curcumin intervenes with SOD-induced EMT in pancreatic cancer and the underlying mechanism...
March 1, 2018: International Journal of Oncology
Mustafa Aziz Hatiboglu, Abdurrahim Kocyigit, Eray Metin Guler, Kerime Akdur, Arife Nalli, Ersin Karatas, Saffet Tuzgen
BACKGROUND: Prognosis of patients with melanoma brain metastasis is poor despite various chemotherapeutic agents. Researchers focus on finding effective treatment with low risk of toxicity. Thymoquinone (TQ) has been found to be effective on different types of cancer. However, no data exists on the effect of TQ in intracerebral melanoma. The purpose of this study was to assess the effect of TQ in B16-F10 melanoma cell in vitro and intracerebral melanoma in vivo. METHODS: The mechanisms of efficacy were investigated by ATP assay for cytotoxicity, flow cytometry and Acridine-orange staining for apoptosis, Comet assay for genotoxicity, CM-H2 DCF-DA (2,7-dichlorodihydrofluorescein) for intracellular reactive oxygen species (ROS) generation and ELISA methods for inflammatory cytokines...
March 3, 2018: World Neurosurgery
Wanrong Wu, Fulin Liu, Kejia Wu, Yurou Chen, Hanshu Wu, Guo Dai, Wei Zhang
BACKGROUND Lon protease is responsible for degrading proteins injured by oxidation, and has 2 isoforms, located in mitochondria and peroxisomes. Recent research showed that Lon protease was upregulated in different types of human cancer, but the role of Lon peptidase 2, peroxisomal (LONP2) in cancer is not well understood. It is known, however, that in cancer biology, reduction-oxidation is one of the molecular mechanisms involved in tumorigenesis. MATERIAL AND METHODS Oncomine databases and tissue microarrays, initially using immunohistochemistry, were used to analyze LONP2 expression in cervical cancer...
March 4, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Antonietta Rosella Farina, Lucia Cappabianca, Luciana Gneo, Pierdomenico Ruggeri, Andrew Reay Mackay
Alternative TrkAIII splicing characterises advanced stage metastatic disease and post-therapeutic relapse in neuroblastoma (NB), and in NB models TrkAIII exhibits oncogenic activity. In this study, we report a novel role for TrkAIII in signaling ER stress to the mitochondria in SH-SY5Y NB cells that results in glycolytic metabolic adaptation. The ER stress-inducing agents DTT, A23187 and thapsigargin activated the ER stress-response in control pcDNA SH-SY5Y and TrkAIII expressing SH-SY5Y cells and in TrkAIII SH-SY5Y cells increased TrkAIII targeting to mitochondria and internalisation into inner-mitochondrial membranes...
February 2, 2018: Oncotarget
Yongqiang Cai, Jinping Lu, Faqing Tang
Molecule interacting with CasL 2 (MICAL2), a microtubule associated monooxygenase, is involved in cell growth, axon guidance, vesicle trafficking and apoptosis. Recent studies have demonstrated that MICAL2 is highly expressed in tumor and accelerates tumor progression and it is deemed to be a novel tumor-promoting factor. MICAL2 overexpression increases cell proliferation to accelerate tumor growth, and MICAL2 also promotes epithelial-mesenchymal transition (EMT)-related proteins to increase cancer cell metastasis...
2018: Journal of Cancer
Guanyi Wang, Dawei Zhang, Shengcai Yang, Yalin Wang, Zhaohui Tang, Xueqi Fu
Prostate cancer is a typical malignant disease with a high incidence and a poor prognosis. Doxorubicin hydrochloride (DOX·HCl) is one of the most effective agents in the treatment of prostate cancer, but severe side effects and metastasis after its treatment impose restrictions on its application. Herein, a combination of genistein (GEN) and doxorubicin-loaded polypeptide nanoparticles (DOX-NPs) is constructed for the treatment of prostate cancer. The DOX-NPs can reduce the side effects caused by free DOX·HCl and produce a relatively low level of intracellular reactive oxygen species (ROS)-induced oxidative damage, while GEN, an inhibitor of the oxidative DNA repair enzyme apurinic/apyrimidinic endonuclease1 (APE1), can further amplify the ROS-induced oxidative damage by downregulating the intracellular expression of APE1 and reducing oxidative DNA repair in the prostate cancer cells...
February 26, 2018: Biomaterials Science
Ron Mittler, Merav Darash-Yahana, Yang Sung Sohn, Fang Bai, Luhua Song, Ioav Zvi Cabantchik, Patricia Jennings, Jose Onuchic, Rachel Nechushtai
SIGNIFICANCE: Cancer cells accumulate high levels of iron and reactive oxygen species (ROS) to promote their high metabolic activity and proliferation rate. However, high levels of iron and ROS can also lead to enhanced oxidative stress and the activation of cell death pathways such as apoptosis and ferroptosis. This has led to the proposal that different drugs that target iron and/or ROS metabolism could be used as anticancer drugs. However, due to the complex role iron and ROS play in cells, the majority of these drugs yielded mixed results, highlighting a critical need to identify new players in the regulation of iron and ROS homeostasis in cancer cells...
February 20, 2018: Antioxidants & Redox Signaling
Shang Chen, Yue Zhou, Lichun Zhou, Yanhui Guan, Yu Zhang, Xiuzhen Han
Choroidal neovascularization (CNV) is the hallmark of late-staged wet age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. DMBT, 6,6'-bis(2,3-dimethoxybenzoyl)-α,α-D-trehalose, had been proved that it could suppress tumor angiogenesis and metastasis by inhibiting production of VEGF. But the effects of DMBT on CNV were not known. This study was to investigate effects and mechanisms of DMBT on CNV in vitro and in vivo...
February 14, 2018: Molecular and Cellular Biochemistry
Lian Li, Fangyuan Ren, Chao Qi, Leiqian Xu, Yinshan Fang, Maoli Liang, Jing Feng, Baoyuan Chen, Wen Ning, Jie Cao
BACKGROUND: Recently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated. METHODS: C57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment...
February 12, 2018: Respiratory Research
Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng
Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial-mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation...
February 9, 2018: Cancer Letters
Wei-Wei Luo, Wen-Wen Zhao, Jin-Jian Lu, Yi-Tao Wang, Xiu-Ping Chen
Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays...
January 2018: Chinese Journal of Natural Medicines
Yu Zou, Di Zhao, Chang Yan, Yanpeng Ji, Jin Liu, Jinyi Xu, Yisheng Lai, Jide Tian, Yihua Zhang, Zhangjian Huang
Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety, and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively...
February 9, 2018: Journal of Medicinal Chemistry
Wen Song, Jing Kuang, Chu-Xin Li, Mingkang Zhang, Diwei Zheng, Xuan Zeng, Chuanjun Liu, Xian-Zheng Zhang
Metastasis and recurrence are two unavoidable and intractable problems in cancer therapy, despite of various robust therapeutic approaches. Currently, it seems that immunotherapy is an effective approach to solve the problems, but the high heterogeneity of tumor tissue, inefficient presentation of tumor antigen and deficient targeting ability of therapy usually blunt the efficacy of immunotherapy and hinder its clinical application. Herein, an approach based on combining photodynamic and immunological therapy was designed and developed...
February 8, 2018: ACS Nano
Islam M D Sodrul, Chenying Wang, Xiangfeng Chen, Jing Du, Hongxiang Sun
Cancer is still a global public health problem, which is the leading cause of death in most countries. Ginseng has been used for centuries all over the world as a panacea that promotes longevity. As the king of herb plants, ginseng holds great promise as a new treatment option which is used either by itself or in combination with other medicinal ingredients that is widely accepted as complementary and alternative medicine in cancer therapy. Ginsenosides, the major pharmacologically active ingredients of ginseng, have been shown to have multiple medicinal effects including prominent anticancer activity...
January 5, 2018: Oncotarget
Caiyan Zhao, Yujia Tong, Xianlei Li, Leihou Shao, Long Chen, Jianqing Lu, Xiongwei Deng, Xuan Wang, Yan Wu
In drug delivery, the poor tumor perfusion results in disappointing therapeutic efficacy. Nanomedicines for photodynamic therapy (PDT) greatly need deep tumor penetration due to short lifespan and weak diffusion of the cytotoxic reactive oxygen species (ROS). The damage of only shallow cells can easily cause invasiveness and metastasis. Moreover, even if the nanomedicines enter into deeper lesion, the effectiveness of PDT is limited due to the hypoxic microenvironment. Here, a deep penetrating and oxygen self-sufficient PDT nanoparticle is developed for balanced ROS distribution within tumor and efficient cancer therapy...
February 6, 2018: Small
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