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Mai Maher, Asmaa E Kassab, Ashraf F Zaher, Zeinab Mahmoud
A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC50 = 1.74 μM. It also exhibited promising potent anticancer activity against ACHN cell line with IC50 value 5.53 μM, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC50 = 4...
December 2019: Journal of Enzyme Inhibition and Medicinal Chemistry
Gang Wang, Zi-Jian Zhang, Wen-Gang Jian, Pan-Hong Liu, Wei Xue, Teng-da Wang, Yu-Yang Meng, Chao Yuan, Hao-Ming Li, Yi-Peng Yu, Zhan-Xin Liu, Qiong Wu, Da-Ming Zhang, Cheng Zhang
BACKGROUND: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC). METHODS: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples...
January 22, 2019: Molecular Cancer
Guang Chen, Jun Zhou, Jie Chen, Jin Zhu, Shuang-Chun Liu, Xiao-Fei Ding, Qiang Zhang
Both Von Hippel-Lindau tumor suppressor (VHL) and Never-in-mitosis A (NIMA)-related kinase 1 (NEK1) are involved in primary cilium formation, but whether VHL could regulate NEK1 is unknown. Here, we demonstrated that renal cancer cells Caki-1 and ACHN with wild-type VHL expressed lower level of NEK1 than that of VHL-defective cells including 786-O, 769-P and A498 cells. VHL-overexpression down-regulated NEK1 in 769-P cells, while VHL-knockdown up-regulated NEK1 in Caki-1 cells. In addition, we found the hypoxia response element (HRE) in the promoter sequence of NEK1 and hypoxia induced NEK1 expression both in vitro and in vivo...
February 12, 2019: Biochemical and Biophysical Research Communications
Luping Wang, Junyu Wang, Hong Zhao, Guoping Jiang, Xiaojie Feng, Wenxia Sui, Hongling Liu
Clear cell renal cell carcinoma (ccRCC) is the most common type of human malignancies of the urological system. Soyasapogenol B (Soy B), an ingredient of soybean, has been found to exert anti-proliferative activities in vitro in human breast cancer cells. Our current study aimed to evaluate the effectiveness of Soy B against ccRCC. The effect of Soy B on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The effect of Soy B on cell proliferation was determined by colony formation assay. Apoptotic percentage was determined by flow cytometry following annexin V-FITC/propidium iodide (PI) double staining...
January 4, 2019: Naunyn-Schmiedeberg's Archives of Pharmacology
Kuang-Chung Chiang, Chung-Yu Lai, Hui-Ling Chiou, Chia-Liang Lin, Yong-Syuan Chen, Shao-Hsuan Kao, Yi-Hsien Hsieh
Timosaponin AIII (TSAIII) is a steroidal saponin that exerts anticancer activity on various cancer cells. In this study, we explore the effects of TSAIII on renal cell carcinoma (RCC) cells. Our findings show that TSAIII treatment (<8 μM) insignificantly influenced cell viability and cell cycle distribution of human RCC cell lines 786-O, A-498, and ACHN. Further observations revealed that TSAIII inhibited migration and invasion of 786-O and A-498 cells, as well as significantly decreased the production and expression of cathepsin C (CTSC) in both the cell types...
January 3, 2019: Journal of Cellular Physiology
Jing Quan, Xiang Pan, Yawen Li, Yimin Hu, Lingzhi Tao, Zuwei Li, Liwen Zhao, Jingyao Wang, Hang Li, Yulin Lai, Liang Zhou, Canbin Lin, Yaoting Gui, Jing Ye, Fangting Zhang, Yongqing Lai
BACKGROUND: Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. METHODS: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC...
December 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shiho Ueda, Hidemi Hayashi, Takako Miyamoto, Shinya Abe, Kana Hirai, Kanji Matsukura, Hideki Yagi, Yuta Hara, Kinji Yoshida, Shogo Okazaki, Masakazu Tamura, Yuki Abe, Toshinori Agatsuma, Shin-Ichiro Niwa, Kazue Masuko, Takashi Masuko
L-type amino-acid transporter 1 (LAT1) disulfide-linked to the CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In this study, we developed novel anti-LAT1 mAbs, and demonstrated the internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody-dependent cellular cytotoxicity, as well as in vivo anti-tumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side effects of anti-human LAT1 mAbs in clinical trials...
December 10, 2018: Cancer Science
Chao Song, Yunhe Xiong, Wenbiao Liao, Lingchao Meng, Sixing Yang
Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and migration-related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses...
December 8, 2018: Journal of Cellular Physiology
Ancy D Nalli, Lauren E Brown, Cheryl L Thomas, Thomas J Sayers, John A Porco, Curtis J Henrich
Rocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells...
November 30, 2018: Scientific Reports
Li-Fang Liu, Ming-Jun Yao, Man-Yu Li, Xiao-Zhen Wu, Cheng-Shan Yuan
Three new iridoids, (rel-4aS,7S,7aS)-1,4a,5,6,7,7a-hexahydro-7-hydroxyl-7-methyl-cyclopenta[c]pyran-4-carboxaldehyde (1), 1,3,5,6-tetrahydro-1-methoxyl-7-methyl-cyclopenta[c]pyran-4-carboxaldehyde (2), and (rel-1R,4S,4aS,7R,7aR)-7-methylhexahydro-1,4-(epoxymethano)cyclopenta[c]pyran-3(1H)-one(3), together with seven known analogues, were isolated from the 95% EtOH extract of the whole plant of Pedicularis uliginosa Bunge.Their structures were elucidated via their extensive NMR spectroscopy and mass spectral data...
November 23, 2018: Chemistry & Biodiversity
Mi-Yeon Jeon, Kyoung-Jin Min, Seon Min Woo, Seung Un Seo, Yung Hyun Choi, Sang Hyun Kim, Dong Eun Kim, Tae-Jin Lee, Shin Kim, Jong-Wook Park, Taeg Kyu Kwon
Maritoclax, an active constituent isolated from marine bacteria, has been known to induce Mcl-1 downregulation through proteasomal degradation. In this study, we investigated the sensitizing effect of maritoclax on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. We found that combined treatment with maritoclax and TRAIL markedly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung cancer (A549) and hepatocellular carcinoma (SK-Hep1) cells...
November 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jie Xu, Bisheng Huang, Saiyang Li, Xiaolu Zhang, Tiancheng Xie, Yunfei Xu
The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) has been reported to serve an important role in a number of human malignancies and is correlated with poor prognosis. However, little is known about the role of LETM1 in renal cell carcinoma (RCC). In the present study, the expression levels of LETM1 were investigated in RCC cell lines (Caki-1, 786-O, OS-RC-2, A498 and ACHN) and the HK-2 normal human renal tubular epithelial cell line. Short interfering RNA (siRNA) was used to knock down the expression of LETM1 in 786-O and A498 cells...
November 2018: Oncology Letters
Yan-Feng Cao, Shi-Feng Wang, Xi Li, Yan-Ling Zhang, Yan-Jiang Qiao
BACKGROUND: Cancer is the second most common cause of death globally. The anticancer effects of Tanshinone IIA (Tan IIA ) has been confirmed by numerous researches. However, the underlying mechanism remained to be integrated in systematic format. Systems biology embraced the complexity of cancer; therefore, a system study approach was proposed in the present study to explore the anticancer mechanism of Tan IIA based on network pharmacology. METHOD: Agilent Literature Search (ALS), a text-mining tool, was used to pull protein targets of Tan IIA ...
October 29, 2018: BMC Systems Biology
Kei Ishibashi, Tomoyuki Koguchi, Kanako Matsuoka, Akifumi Onagi, Ryo Tanji, Ruriko Takinami-Honda, Seiji Hoshi, Mitsutaka Onoda, Yoshimasa Kurimura, Junya Hata, Yuichi Sato, Masao Kataoka, Soichiro Ogawsa, Nobuhiro Haga, Yoshiyuki Kojima
Metastatic renal cell carcinoma (mRCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKIs), the novel targeted agents have been used for the treatment of mRCC and have shown efficacy. Interferon (IFN)-α is also one of the most frequently used agents in immunotherapy. However, drug resistance needs to be overcome to achieve a sufficiently positive effect. Interleukin-6 (IL-6), which induce suppressor of cytokine signaling-3 (SOCS3) expression, is one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC)...
October 23, 2018: Fukushima Journal of Medical Science
Dongming Chen, Meng Zhu, Huang Su, Jiexun Chen, Xianlin Xu, Changchun Cao
Recently, long noncoding RNA have been identified as new gene regulators and prognostic biomarkers in various cancers, including renal cell carcinoma (RCC). The expression and biological roles of LINC00961 have been reported in many human cancers. However, up to date, no study of LINC00961 has been shown in RCC. Currently, we aimed to investigate the function of LINC00961 in RCC progression. Interestingly, we observed that LINC00961 could act as a novel biomarker in predicting the diagnosis of RCC. Then, we found that LINC00961 was greatly downregulated in RCC cell lines (Caki-1, Caki-2, 786-O, A498, and ACHN cells) compared with normal renal cell lines (HK-2 cells)...
October 26, 2018: Journal of Cellular Physiology
Yanxiang Shao, Zhenhua Liu, Jianbang Liu, Haizhou Wang, Long Huang, Tianhai Lin, Jiyan Liu, Qiang Wei, Hao Zeng, Gu He, Xiang Li
The majority of clear cell renal cell carcinomas (ccRCCs) are caused by an accumulation of hypoxia‑inducible factor (HIF) and the overexpression of downstream genes in response to the von Hippel‑Lindau (VHL) gene becoming inactivated. In the present study, our hypothesis was that BNIP3, a gene positioned downstream of HIF, would be expressed at a higher level in ccRCC; however, instead, lower levels of BNIP3 expression were identified in RCC tumor tissues compared with adjacent non‑tumor tissues. These changes were associated with lower levels of VHL, and higher levels of HIF and vascular endothelial growth factor...
October 24, 2018: International Journal of Oncology
J Sun, W D Song, S Y Yan, Z J Xi
OBJECTIVE: To determine whether chloroquine (CQ), an often used inhibitor of late autophagy and autophagosome/lyosome fusion, can inhibit proliferation of renal carcinoma cells and investigate its effect on sunitinib (ST)-induced apoptosis. METHODS: Renal carcinoma cell line 786 O and ACHN had been used as cellular model and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was carried out to detect the cell viability in response to CQ or ST treatment...
October 18, 2018: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Liwen Zhao, Jing Quan, Zuwei Li, Xiang Pan, Jingyao Wang, Jinling Xu, Weijie Xu, Xin Guan, Hang Li, Shangqi Yang, Yaoting Gui, Yun Chen, Yongqing Lai
The aim of the present study was to investigate the role of microRNA (miR)‑222‑3p in renal cell carcinoma (RCC). The expression level of miR‑222‑3p was detected in RCC tissues and cell lines (ACHN, 786‑O, Caki‑1 and 769‑P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK‑2 cells. Further in vitro experiments demonstrated that the over-expression of miR‑222‑3p promoted the migration and invasion, and attenuated the apoptosis of 786‑O cells, whereas the knockdown of miR‑222‑3p suppressed the migration and invasion and induced the apoptosis of 786‑O cells...
October 15, 2018: International Journal of Molecular Medicine
Lei Liu, Qifei Wang, Jun Mao, Tao Qin, Yan Sun, Jinfeng Yang, Yanyan Han, Lianhong Li, Quanlin Li
Metastatic Renal cell carcinoma (RCC) remains a difficult oncologic challenge. Salinomycin is a monocarboxylic polyether antibiotic, which has been proved to possess anti-tumor activities in multiple types of cancer cells. However, its effects on RCC cells remains unclear. In our study, salinomycin could inhibit the proliferation and viability of RCC cell lines 786-O and ACHN. The TUNEL assay revealed that treatment with salinomycin induced DNA breaking in RCC cells. Consistently, Western blotting showed up-regulation of pro-apoptotic biomarkers (cleaved caspase3/9 and cleaved PARP1) and down-regulation of anti-apoptotic biomarker (survivin) in RCC cells after salinomycin treatment, suggesting that salinomycin could induce RCC cell apoptosis...
September 28, 2018: Chemico-biological Interactions
Yujiao Zhang, Yizeng Fan, Shangke Huang, Guanying Wang, Rui Han, Fuxi Lei, Anqi Luo, Xin Jing, Lin Zhao, Shanzhi Gu, Xinhan Zhao
Thymoquinone (TQ, 2-methyl-5-isopropyl-1,4-benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti-tumor efficiency in various cancers. Autophagy is a self-digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786-O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model...
December 2018: Cancer Science
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