scholarly journals Synthesis, Characterization and Antiproliferative Evaluation of Pt(II) and Pd(II) Complexes with a Thiazine-Pyridine Derivative Ligand

2021 ◽  
Vol 14 (5) ◽  
pp. 395
Author(s):  
Silvia Gutiérrez-Tarriño ◽  
Javier Espino ◽  
Francisco Luna-Giles ◽  
Ana B. Rodríguez ◽  
José A. Pariente ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Drugs ◽  
Platinum Complexes ◽  
Chemotherapeutic Agents ◽  
Pyridine Derivative ◽  
Cervix Carcinoma ◽  
Multinuclear Complexes ◽  
Histiocytic Lymphoma ◽  
Ovary Adenocarcinoma

Chemical, pharmacological, and clinical research on anticancer coordination complexes has led to noteworthy anticancer drugs such as cisplatin, carboplatin and oxaliplatin. Although these compounds are effective chemotherapeutic agents in the treatment of different tumors, they are associated with high toxicity and numerous side effects. Several studies have shown that the range of platinum complexes with antitumor activity is not limited to structural analogs of cisplatin. Therefore, the development of convenient anticancer drugs that can be effectively used for the treatment of human tumors has become the main goal of most research groups in this field. In this sense, active platinum complexes without NH groups, transplatinum complexes, multinuclear complexes, cationic complexes, and several classes of palladium(II) complexes have emerged. Herein, the synthesis and characterization of two Pt(II) or Pd(II) complexes with PyTz (2-(2-pyridyl)iminotetrahydro-1,3-thiazine), a thiazine derivative ligand, with the formula [MCl2(PyTz)]·C2H6O (M = Pt(II) or Pd(II)) were reported. The potential anticancer ability of both complexes was evaluated in epithelial cervix carcinoma HeLa, human ovary adenocarcinoma SK-OV-3, human histiocytic lymphoma U-937, and human promyelocytic leukemia HL-60 cell lines. Interestingly, the Pt(II) complex showed great cytotoxic potential against all tumor cell lines tested, whereas the Pd(II) complex displayed slight antitumor actions.

scholarly journals Cflar Splicing SNP As Predictor of Chemo-Sensitivity to Anticancer Drugs

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2056-2056
Author(s):  
Lata Chauhan ◽  
Emilie J Bergsma ◽  
Jatinder K Lamba
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Extrinsic Pathway ◽  
Wide Range

Abstract Background: Anticancer therapeutics leverages activation of apoptosis signal transduction pathways (extrinsic and intrinsic apoptotic pathways) in cancer cells. Apoptosis induced by the extrinsic pathway complements that induced by the intrinsic pathway, so targeting extrinsic pathway is considered a useful new therapeutic approach. Preclinical data suggests TNF related apoptosis inducing ligand (TRAIL) as a promising approach as apoptosis of tumor cells is achievable in vivo without lethal toxicities. CASP8 and FADD-like apoptosis regulator (CFLAR) is an inhibitor of death receptor signaling that inhibits TRAIL-mediated caspase 8 auto-activation and subsequent apoptosis. We recently identified a splicing single nucleotide polymorphism (SNP) rs10190751 G>A in CFLAR, where presence of the variant allele (A) was associated with alternate splicing as well as with chemo-sensitivity to chemotherapeutic agent triptolide. However role of CFLAR and the splicing SNP on chemo-sensitivity to wide array of anticancer drugs is not known. Objective: Given the central role of CFLAR in apoptotic pathway, the goal of this study was to investigate impact of CFLAR and its splicing SNP on cytotoxicity of wide range of chemotherapeutic drugs including the ones extensively used in hematological malignancies. Methods: We selected chemotherapeutic agents with wide range of mechanisms of action as blocking DNA biosynthesis, interfering with structure or function of DNA or protein synthesis, interfering with DNA transcription or replication as well as drugs that are cell cycle specific or not. We selected nine Epstein-Barr-virus transformed lymphoblastoid cell lines (LCLs) that are part of International HapMap project representing different genotype for rs10190751 (CFLAR splicing polymorphism; 3 in each genotype category) with twelve different chemotherapeutic agents. Further validation of CFLAR's role in in vitro chemosensitivity was evaluated using CFLAR knockdown and overexpression studies in pancreatic and leukemic cell lines such as Panc-1 and THP1. Results: CFLAR splicing SNP rs10190751, was associated with in vitro cytotoxicity of several chemotherapeutic agents (Bortezomib, SAHA, doxorubicin, sorafenib). The results of screening of 122 FDA approved drugs and their relation with CFLAR as well as its splicing SNP will be presented at the annual meeting. As an example we show below that knock down of CFLAR isoforms have a significant impact on in vitro chemosensitivity to bortezomib and SAHA (Figure 1) Conclusion: Our results suggest critical role of CFLAR in anticancer drug mediated cell death. Additionally splicing SNP in CFLAR seems to play an important role in drug sensitivity/resistance. Therapeutic strategies to directly or indirectly inhibit the expression and/or function of CFLAR might be an attractive option to overcome resistance to wide range of chemotherapeutic agents. Figure 1. Impact of siRNA mediated knockdown or of CFLAR on Bortezomib and SAHA sensitivity in THP1 and Panc-1 cancer cell line. Figure 1. Impact of siRNA mediated knockdown or of CFLAR on Bortezomib and SAHA sensitivity in THP1 and Panc-1 cancer cell line. Disclosures No relevant conflicts of interest to declare.

scholarly journals Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Ching Huang ◽  
Tien-Ming Yuan ◽  
Bang-Hung Liu ◽  
Kai-Li Liu ◽  
Chiung-Hua Wung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Anticancer Drugs ◽  
Apoptotic Cell ◽  
Squamous Carcinoma ◽  
Chemotherapeutic Agents ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

The ability of capsaicin co-treatment to sensitize cancer cells to anticancer drugs has been widely documented, but the detailed underlying mechanisms remain unknown. In addition, the role of ribophorin II turnover on chemosensitization is still uncertain. Here, we investigated capsaicin-induced sensitization to chemotherapeutic agents in the human oral squamous carcinoma cell lines, HSC-3 and SAS. We found that capsaicin (200 μM) did not induce remarkable apoptotic cell death in these cell lines; instead, it significantly enhanced autophagy with a concomitant decrease of ribophorin II protein. This capsaicin-induced decrease in ribophorin II was intensified by the autophagy inducer, rapamycin, but attenuated by the autophagy inhibitors, ULK1 inhibitor and chloroquine, indicating that the autophagic process was responsible for the capsaicin-induced down-regulation of ribophorin II. Co-administration of capsaicin with conventional anticancer agents did, indeed, sensitize the cancer cells to these agents. In co-treated cells, the induction of apoptosis was significantly reduced and the levels of the necroptosis markers, phospho-MLKL and phospho-RIP3, were increased relative to the levels seen in capsaicin treatment alone. The levels of DNA damage response markers were also diminished by co-treatment. Collectively, our results reveal a novel mechanism by which capsaicin sensitizes oral cancer cells to anticancer drugs through the up-regulation of autophagy and down-regulation of ribophorin II, and further indicate that the induction of necroptosis is a critical factor in the capsaicin-mediated chemosensitization of oral squamous carcinoma cells to conventional anticancer drugs.

scholarly journals Inhibitory Effect of 2′-Substituted Nucleosides on Hepatitis C Virus Replication Correlates with Metabolic Properties in Replicon Cells

2005 ◽  
Vol 49 (5) ◽  
pp. 2050-2058 ◽  
Author(s):  
Joanne E. Tomassini ◽  
Krista Getty ◽  
Mark W. Stahlhut ◽  
Sung Shim ◽  
Balkrishen Bhat ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Lines ◽  
Growth Period ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Metabolic Properties ◽  
Ns5b Polymerase

ABSTRACT Nucleosides have been widely used in the treatment of viral diseases, but relatively few have been identified as inhibitors of hepatitis C virus (HCV). The modified ribonucleosides, 2′-C-methyl-adenosine and 2′-O-methyl-cytidine, are potent inhibitors of HCV replication which specifically target the NS5B polymerase. Herein, a more extensive characterization of the effect of these compounds upon HCV replication in subgenomic replicons is reported. A highly selective antireplicative effect induced by the nucleosides in replicon-containing cell lines was maintained during an exponential growth period with potencies which paralleled the reduction of both positive- and negative-strand RNA replication. Moreover, the inhibitory effect closely correlated with the intrinsic metabolic properties of differing replicon clonal lines. Interestingly, while 2′-C-methyl-adenosine elicited similar inhibitory potencies in different cell lines, 2′-O-methyl-cytidine was found to be inactive in one replicon cell line tested, although the corresponding triphosphates comparably inhibited the in vitro activity of replication complexes isolated from these cells and the activity of NS5B polymerase using synthetic templates. The lack of antireplicative effect, attributed to poor intracellular conversion of the 2′-O-methyl-cytidine nucleoside to the active 5′-triphosphate, was reversed using a monophosphate prodrug. Thus, although replicon cells are useful for evaluating the effect of inhibitors upon HCV replication, these findings have important implications for their use in the identification and characterization of nucleosides and other chemotherapeutic agents requiring cellular metabolism.

Characterization of pituitary-derived cell lines, Tpit/E, Tpit/F1 and TtT/GF

2014 ◽  
Author(s):  
Naoto Nishimura ◽  
Saishu Yoshida ◽  
Masashi Higuchi ◽  
Hideji Yako ◽  
Hiroki Ueharu ◽  
...  
Keyword(s):  
Cell Lines

Characterization of Healthy and Tumor Oral Cell Lines of Human Origin. The preliminary stage in the assessment of relevant chemical compounds with impact on dentistry

2018 ◽  
Vol 69 (10) ◽  
pp. 2889-2894
Author(s):  
Ion Virgil Corlan ◽  
Adelina Cheveresan ◽  
Delia Berceanu Vaduva ◽  
Cristian Nica ◽  
Alin Faur ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Chemical Compounds ◽  
Tongue Squamous Cell Carcinoma ◽  
Gingival Fibroblasts ◽  
Human Origin ◽  
Preliminary Stage

The present study was aimed to evaluate the confluence percentage of three oral cell lines, namely primary gingival keratinocytes (PGK), primary gingival fibroblasts (HGF) and tongue squamous cell carcinoma (SCC-4). All cells have been monitored at different passages for 21 days. Evaluation of confluence percentage reveals the fact that primary gingival keratinocytes and tongue squamous cell carcinoma at small passages requires a period of about two weeks to reach a confluence of approximately 80% while for the gingival fibroblasts a period of about three times smaller is satisfactory.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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