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Bcl-2 inhibitors

Jun-Ming Chen, Jue Zhang, Yong-Mei Xia, Xiao-Xia Wang, Jian Li
Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5-fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5-fluorouracil. The mechanism of this anticancer activity is also investigated...
April 2018: Oncology Letters
Xinghua Wei, Weiwei Zeng, Keji Xie, Pengfei Diao, Ping Tang
Although it is the most widely used biomarker for prostate cancer, the use of prostate specific antigen (PSA) is controversial due to its limitations in specificity and sensitivity. The proteasome is a complex associated with cell proliferation and apoptosis, and the abnormity of these processes may lead to tumor occurrence. Previous studies have reported that proteasomal activity is associated with cancer progression and can be used in risk stratification. The purpose of the present study was thus to investigate the feasibility of proteasome activity as a biomarker for prostate cancer...
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
Qiu-Shuang Wang, Shi-Qiang Shen, Hua-Wen Sun, Zhi-Xiang Xing, Hou-Lai Yang
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males. In this work, we aim to investigate the possible anti-cancer effects of interferon-gamma (IFN-γ) in CRC cells. We observed that IFN-γ induced mitochondria-derived reactive oxygen species (ROS) production in a time-dependent manner in SW480 and HCT116 cell lines. The IFN-γ-induced mitochondrial ROS generation was dependent on the activation of cytosolic phospholipase A2 (cPLA2). In addition, a mitochondria-targeted antioxidant SS31 and/or cPLA2 inhibitor AACOCF3 abolished the IFN-γ-induced ROS production and subsequent autophagy and apoptosis...
March 15, 2018: Biochemical and Biophysical Research Communications
Wenqian Zhang, Ying Cui, Junling Gao, Ran Li, Xiaohua Jiang, Yanxia Tian, Kaijie Wang, Jianzhong Cui
BACKGROUND This study aimed to investigate the potential neuroprotective effect of recombinant osteopontin (r-OPN) on apoptotic changes via modulating phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK-3β) signaling in a rat model of intracerebral hemorrhage (ICH). MATERIAL AND METHODS We subjected 10-12-week-old Sprague-Dawley male rats (n=120) to injection of autologous blood into the right basal ganglia to induce ICH or sham surgery. ICH animals received vehicle administration, r-OPN (4 μL/pup), or r-OPN combined with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (86 ng/pup) at 30 min after injury...
March 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Sheng Peng, Hong-Zhu Yan, Pei-Rong Liu, Xiao-Wei Shi, Chun-Liang Liu, Qi Liu, Yu Zhang
BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry...
March 13, 2018: Cellular Physiology and Biochemistry
Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
Huan Gao, Yue Zhang, Lei Dong, Xiao-Yu Qu, Li-Na Tao, Yue-Ming Zhang, Jing-Hui Zhai, Yan-Qing Song
To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway...
April 2018: Experimental and Therapeutic Medicine
Tao Wang, Hui Zhao, Hua Gao, Changming Zhu, Yao Xu, Liping Bai, Junbo Liu, Feng Yan
The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are activated during pathogenesis of gastrointestinal stromal tumors (GISTs). Forkhead box protein O1 (FOXO1) is a transcription factor regulated by the MAPK and PI3K pathways and is associated with multiple metabolic reactions. The present study aims to investigate the association of FOXO1 with cell proliferation and apoptosis in the cell line, GIST-T1. Cell counting kit-8 assay revealed that cell growth was inhibited by the PI3K inhibitor, LY294002, and/or MAPK inhibitor, UO126...
April 2018: Experimental and Therapeutic Medicine
Shuko Hakata, Jun Terashima, Yu Shimoyama, Kouji Okada, Shiho Fujioka, Erika Ito, Wataru Habano, Shogo Ozawa
Irinotecan (CPT-11) is a key therapeutic drug used in the treatment of colorectal cancer, although acquired or constitutive resistance to CPT-11 (and its activated metabolite SN-38) can lead to tumor progression. Since the acquisition of drug resistance can result from DNA hypermethylation, the antitumor activity of CPT-11 and SN-38 was assessed in combination with a known DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, also known as decitabine (DAC). DAC potentiated the antitumor activity of CPT-11 additively, and that of SN-38 synergistically, as measured by colony formation in the human colorectal cancer HCT116 cell line...
April 2018: Oncology Letters
Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Cheng Zeng, Wen Jiang, Ruifang Zheng, Chenghui He, Jianguang Li, Jianguo Xing
Our previous research demonstrated that tilianin protects the myocardium in a myocardial ischemia reperfusion injury (MIRI) rat model and has prominent pharmacological potential as a cardiovascular drug. Our study aimed to investigate the molecular signaling implicated in the improvement of myocardial survival induced by tilianin, a flavonoid antioxidant. Tilianin (2.5, 5, and 10 mg/kg/d) or saline was orally administered to rats for 14 days. On the 15th day, ischemia was induced by ligating the left anterior descending artery for 45 min, followed by 4 h of reperfusion...
2018: PloS One
Matharage Gayani Dilshara, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Ilandarage Menu Neelaka Molagoda, Jin-Woo Jeong, Seungheon Lee, Sang Rul Park, Gi-Young Kim, Yung Hyun Choi
In this study, we addressed how silibinin enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in various cancer cells. Combined treatment with silibinin and TRAIL (silibinin/TRAIL) induced apoptosis accompanied by the activation of caspase-3, caspase-8, caspase-9, and Bax, and cytosolic accumulation of cytochrome c. Anti-apoptotic proteins such as Bcl-2, IAP-1, and IAP-2 were inhibited as well. Silibinin also triggered TRAIL-induced apoptosis in A549 cells through upregulation of death receptor 5 (DR5)...
February 13, 2018: Oncotarget
Bibi Kulsoom, Tahir Sultan Shamsi, Nasir Ali Afsar, Zahida Memon, Nikhat Ahmed, Syed Nazrul Hasnain
Purpose: Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy...
2018: Cancer Management and Research
Xiaohua Wang, Cheng Chen, Guoren Zhou, Jinjun Ye, Rong Yin, Dongjie Feng, Shuai Zhang, Xiaojun Wang, Xin Zhao, Zhi Zhang
BACKGROUND/AIMS: Our previous study suggested the anti-tumor activity of sepia ink oligopeptide (SIO). Here we sought to investigate the underlying molecular mechanism. METHODS: Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by Annexin V/Propidium Iodide (PI) staining. The mitochondria pathway was characterized by quantification of Bcl-2, Bax, Caspase-9 and Cyto-C. The death receptor pathway was analyzed by determinement of Fas, Caspase-8 and NIK...
March 7, 2018: Cellular Physiology and Biochemistry
Feng Li, Laura E Pascal, Jianhua Zhou, Yibin Zhou, Ke Wang, Anil V Parwani, Rajiv Dhir, Peng Guo, Dalin He, Joel B Nelson, Zhou Wang
The mechanisms involved in the development of benign prostatic hyperplasia (BPH) are poorly understood. One potential mechanism involved in BPH pathogenesis may involve altered expression of genes related to apoptosis and proliferation because reduced cell death and increased proliferation are thought to contribute to prostatic enlargement. This study examined the expression of B-cell lymphoma 2 (BCL-2) and B-cell lymphoma-extra large (BCL-XL), two important anti-apoptosis factors that are also capable of inhibiting cell proliferation via accelerated G1 arrest or delayed G1/S transition, using immunostaining in simple prostatectomy BPH specimens from patients naïve to androgen manipulation...
2018: American Journal of Clinical and Experimental Urology
Clarence T Sasaki, Sotirios G Doukas, Dimitra P Vageli
PURPOSE: Bile-containing gastroesophageal reflux may promote cancer at extraesophageal sites. Acidic bile can accelerate NF-κB activation and molecular events, linked to premalignant changes in murine hypopharyngeal mucosa (HM). We hypothesize that short-term in vivo topical application of NF-κB inhibitor BAY 11-7082 can prevent acidic bile-induced early preneoplastic molecular events, suggesting its potential role in disease prevention. EXPERIMENTAL DESIGN: We topically exposed HM (C57Bl/6j wild-type) to a mixture of bile acids at pH 3...
March 9, 2018: Neoplasia: An International Journal for Oncology Research
Nahla Reda Sarhan, Nesreen Moustafa Omar
Tadalafil (Cialis) is one of the most commonly used phosphodiesterase type5 (PDE5) inhibitors. This work aimed to analyze the histological and ultrastructural changes provoked by chronic tadalafil administration in the rat retina, correlate between such changes and PDE5 immunoexpression and to evaluate the possible reversibility of these changes. Thirty Sprague Dawley male rats were randomly distributed into 3 groups. Control group; given 1 ml distilled water daily for 6 weeks. Tadalafil group; given tadalafil in a daily dose of 2...
March 8, 2018: Acta Histochemica
Jong-Woon Shin, Sae-Bom Kwon, Yesol Bak, Sang-Ku Lee, Do-Young Yoon
The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53...
March 28, 2018: Science China. Life Sciences
Zhaojun Shen, Saisai Li, Bo Sheng, Qi Shen, Lu-Zhe Sun, Haiyan Zhu, Xueqiong Zhu
BACKGROUND: Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. METHODS: Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University...
March 9, 2018: Journal of Translational Medicine
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