• Title/Summary/Keyword: Drug-associated

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Can Cancer Therapy be Achieved by Bridging Apoptosis and Autophagy: a Method Based on microRNA-Dependent Gene Therapy and Phytochemical Targets

  • Vijayarathna, Soundararajan;Gothai, Sivapragasam;Jothy, Subramanion L;Chen, Yeng;Kanwar, Jagat R;Sasidharan, Sreenivasan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7435-7439
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    • 2015
  • A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.

Apoptosis of Colorectal Cancer UTC116 Cells Induced by Cantharidinate

  • Liu, Bin;Gao, Hai-Cheng;Xu, Jing-Wei;Cao, Hong;Fang, Xue-Dong;Gao, Hai-Mei;Qiao, Shi-Xing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3705-3708
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    • 2012
  • Effects of Cantharidinate on apoptosis of human colorectal cancer UTC-116 cells were investigated by means of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, H and E staining, flow cytometry, and Raman Spectra analysis. The results showed Cantharidinate to exert inhibitory action on proliferation of human colorectal cancer UTC-116 cells, inducing apoptosis, arresting cells in G1 phase, with decline of S and G2 phases. In addition, the results of Raman spectrum showed significant changes in the UTC-116 cells chemical structure with stretching after the application of Cantharidinate. Taken together, these results suggest that the treatment of human colorectal cancer with Cantharidinate may be associated with multiple molecular mechanisms for apoptosis. Furthermore, similar to fluorouracil, Cantharidinate should be considered as novel assistant drug for controlling the growth of human colorectal cancer UTC-116 cells.

HQSAR Study on Imidazo[1,2-b]pyridazine Derivatives as p38 MAP Kinase Antagonists

  • Bhujbal, Swapnil P.;Keretsu, Seketoulie;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.11 no.2
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    • pp.107-112
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    • 2018
  • p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model ($q^2=0.522$, SDEP=0.479, NOC=5, $r^2=0.703$, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

Clinical Application of Ma Huang in the Obesity Treatment (비만처방에서 마황의 임상활용에 대한 고찰;용량, 효과, 부작용 등의 측면에서)

  • Song, Yun-Kyung;Lim, Hyung-Ho
    • Journal of Korean Medicine for Obesity Research
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    • v.7 no.1
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    • pp.1-7
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    • 2007
  • Background : Use of Ma Huang is controversial. Multiple reports of adverse effects led the U.S. Federal Drug Administration (FDA) to announce about prohibiting dietary supplements containing ephedrine alkaloids/Ma Huang. Objective : The objective of the study was to review the evidence from literature and rigorous clinical trials on the dosage, effectiveness, and adverse effects. Methods : Literature searches were conducted in U.S. FDA database after 2003 and digital Uibujeonok(醫部全錄). Hand searches of medical journal and bibliographies of identified articles were conducted. Results : Ma Huang has been used in Korean Oriental Medicine to treatment asthma and other ailments. Recently, Ephedrine/Ma Huang are used for weight loss or to enhance athletic performance in Europe and America, Korea. Ephedrine/Ma Huang are associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. In addition to that, a risk of serious adverse events, including heart attack, stroke, epilepsy and psychiatric problem are also have been reported. Therefore, max dose of total alkaloids of ephedrine is studied in need of a specialist's part. Conclusion : In most reports, Ma Huang effectively promoted short-term weight loss and enhancement of athletic performance, But, safety with long-term use requires further investigation.

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A Case of Hemolytic Uremic Syndrome Induced by Pneumococcal Infection (폐구균 감염으로 유발된 용혈성 요독 증후군 ( Hemolytic Uremic Syndrome) 1례)

  • Sim Yoon-Hee;Choi Eung-Sang;Lim In-Seok
    • Childhood Kidney Diseases
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    • v.6 no.2
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    • pp.237-242
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    • 2002
  • Hemolytic Uremic Syndrome (HUS) is the most common cause of acute renal failure in children and is comprised of the combination of hemolytic anemia, thrombocytopenia, and acute renal failure. Atypical HUS, rare in childhood, has worse prognosis than that of typical HUS and is associated with chemotherapy drug, other bacterial (especially Streptococcus pneumoniae) or viral infections, and so on. We report a case of HUS caused by pneumococcal infection in 4-year-old boy. While he was admitted with pneumonia and pleural effusion, pneumococcal infection could be revealed. Although HUS progressed rapidly, he immediately received 3-time hemodialysis and recovered completely after two weeks.

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Effects on the Apoptosis of U937 cell line by n-butanol Extracts of Drynariae Rhizoma (골쇄보(骨碎補) 부탄올 추출물의 U937세포주 세포자멸사에 미치는 효과)

  • Cho, Sung-Yeon;Jeong, Han-Sol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.2
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    • pp.358-364
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    • 2006
  • To investigate the possible mechanism of Drynariae Rhizoma extracts as a candidate of anti-cancer drug, I examined the effects of Drynariae Rhizoma extracts on the apoptosis of U937 cell line. MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. Drynariae Rhizoma extracts treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with induction of apoptotic cell death. Drynariae Rhizoma extracts treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. RT-PCR data revealed that the level of bcl-2, bcl-xL mRNA expressions decreased in a dose-dependent manner. These findings suggest that Drynariae Rhizoma extracts may have induction of apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.

Studies on the Metabolism of Sinigrin in Rat (흰쥐에서 sinigrin 대사에 관한 연구)

  • Huh, Keun;Shin, Uk-Seob;Lee, Sang-Il;Song, Min-Ik
    • Biomolecules & Therapeutics
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    • v.2 no.1
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    • pp.11-15
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    • 1994
  • The detoxifying properties of cruciferous vegetables components have been the subject of several recent investigations. Evidences from many biochemical and pharmacological studies indicated that higher consumption of cruciferous vegetables is associated with lower incidence of harmful actions such as hepatotoxicity and oxidative stress in animal and human populations. Recently, it has been reported that drug metabolizing and detoxifying enzyme activities were increased by cruciferous vegetable extract in which sinigrin is known to be a main active component, accounting for about 2 to 3 percents of total extract. The detoxifying effect of sinigrin has been well reported in several literatures. The metabolism of sinigrin in animal, however, has not been reported yet. That led us to study the metabolism of sinigrin in rat. Sinigrin is nown to be metabolized into three compounds, i.e., allyl isothiocyanate, glucose and potassium phosphate in cruciferous vegetables. Allyl isothiocyanate was formed in rat hepatic mitochondrial fraction in dose and incubation time dependent manner, that was confirmed by HPLC. Glucose formation was came up with results similar to that of allyl isothiocyanate. Three hours after i.p. administration of sinigrin to rat, allyl isothiocyanate appeared in rat liver, and five hours later it was detected in liver and blood. The above results suggested that sinigrin might be metabolized into allyl isothiocyanate, glucose and potassium phosphate in rat.

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Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line

  • Yaghoobi, Hajar;Bandehpour, Mojgan;Kazemi, Bahram
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.299-304
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    • 2016
  • Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.

Garlic Phytocompounds Possess Anticancer Activity by Specifically Targeting Breast Cancer Biomarkers - an in Silico Study

  • Roy, Nabarun;Davis, Sangeetha;Narayanankutty, Arunaksharan;Nazeem, PA;Babu, TD;Abida, PS;Valsala, PA;Raghavamenon, Achuthan C
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2883-2888
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    • 2016
  • Background: Breast cancer (BC) is a serious lifestyle disease. There are several prognostic biomarkers like nuclear receptors whose over-expression is associated with BC characteristics. These biomarkers can be blocked by compounds with anti-cancer potential but selection must be made on the basis of no adverse side effects. This study is focused on finding of compounds from a plant source garlic. Materials and Methods: Twenty compounds from garlic and five targets considered involved in BC were retrieved from Pubchem database and Protein Data Bank respectively. They were docked using Accelrys Discovery Studio (DS) 4.0. The compounds which showed interaction were checked for drug likeliness. Results: Docking studies and ADMET evaluation revealed twelve compounds to be active against the targets. All the compounds displayed highly negative dock scores which indicated good interactions. Conclusions: The results of this study should help researchers and scientists in the pharmaceutical field to identify drugs based on garlic.

Afatinib ameliorates osteoclast differentiation and function through downregulation of RANK signaling pathways

  • Ihn, Hye Jung;Kim, Ju Ang;Bae, Yong Chul;Shin, Hong-In;Baek, Moon-Chang;Park, Eui Kyun
    • BMB Reports
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    • v.50 no.3
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    • pp.150-155
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    • 2017
  • Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor ${\kappa}B$ (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.