Combined therapy of ruthenium dendrimers and anti-cancer drugs against human leukemic cells

2021 ◽  
Author(s):  
Sylwia Michlewska ◽  
Marta Maroto ◽  
Marcin Hołota ◽  
Małgorzata Kubczak ◽  
Natalia Sanz del Olmo ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Leukemic Cells ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Human Leukemic Cells

Carbosilane ruthenium(II) dendrimers have been complexed with conventional anti-cancer drugs. Due to its features, the presence of ruthenium within a dendrimer structure improves the anti-cancer properties of nanocomplexes containing 5-flurouracyl,...

Intracellular concentrations of anti cancer drugs in leukemic cells in vitro vs in vivo

1990 ◽  
Vol 25 (4) ◽  
pp. 252-256 ◽  
Author(s):  
B. Sundman-Engberg ◽  
U. Tidefelt ◽  
J. Liliemark ◽  
C. Paul
Keyword(s):  
Leukemic Cells ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Intracellular Concentrations

Functional Analysis of a Cation Transporter OCT6: A Mediator of the Cellular Influx of Adriamycin.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4374-4374
Author(s):  
Yoko Okitsu ◽  
Hideo Harigae ◽  
Shinichiro Takahashi ◽  
Shori Abe ◽  
Mitsunori Okabe ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Xenopus Oocytes ◽  
Intracellular Concentration ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Clinical Samples ◽  
Dependent Manner ◽  
Cancer Drugs ◽  
Anti Cancer

Abstract (Introduction) It is necessary for killing leukemic cells effectively to achieve a sufficient intracellular concentration of anti-cancer drugs. To date, overexpression of efflux pump such as MDR-1 and MRP-1, which leads to a decrease of cellular concentration of drugs, has been shown to attenuate the therapeutic effect of anti-cancer drugs and correlate with low remission rate in acute leukemia. If the expression of genes, which import anti-cancer drugs, can be induced specifically in leukemic cells, it would lead to an increase of intracellular concentration, resulting in an enhancement of the pharmacological effect. In this study, we performed the pharmacological characterization of a cation transporter gene, OCT6, and explore the possibility of its application for anti-cancer therapy. (Methods) Tissue distribution of OCT6 was examined by Northern blot analysis. Expression in clinical samples that consist of 34 patients; 15 patients with acute lymphoblastic leukemia (ALL), 17 patients with acute myelogenous leukemia (AML), 2 patients with chronic myelogenous leukemia (CML) in blastic crisis, was examined by quantitative RT-PCR. The percentage of blasts in each sample was above 80%. For functional analysis, OCT6 cRNA was injected into Xenopus oocytes and pharmacological analysis was performed. In order to examine the transporting activity in hematopoietic cells, we established subclones of Jurkat, a T lymphocytic leukemia cell line, in which OCT6 gene is constitutively expressed, and the change of the sensitivity for adriamycin was examined. (Result) By Northernblot analysis, 2.4kb OCT6 mRNA was detected in testis and bone marrow in adult tissues. OCT6 expressed in Xenopus oocytes transported not only tetraethlammonium but also adriamycin in a saturable and dose-dependent manner. The apparent Km value for [14C] adriamycin was 5.2±0.4μM. On the other hand, OCT6 did not transport either of methotrexate (MTX) and 5-fluorouracil (5-FU), which are not organic cations. After the exposure of adrimycin at the therapeutic concentration, the viability of OCT6 overexpressing Jurkat cells was significantly decreased compared to that of control cells. Consistent with this, the percentage of apoptosis cells became higher than that of control cells. When the expression level was examined in clinical samples, the average of the levels of patients was comparable to PBMCs. The level of patients, who achieved with complete remission (CR), was slightly higher than that of patients with non-response (NR), but the difference was not significant. Some patients exhibited the high expression of OCT6, but the distribution did not deviated to either CR or NR group. (Conclusion) These results suggest that the induction of OCT6 in leukemic cells might be a novel strategy for leukemia treatment.

Sensitivity of human leukemic cells to anti-cancer agents in culture

1974 ◽  
Vol 23 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Ming Y. Chu ◽  
Marvin L. Hoovis
Keyword(s):  
Leukemic Cells ◽  
Anti Cancer ◽  
Human Leukemic Cells

A Case of Malignant Melanoma Treated with a Combination of Anti-Cancer Drugs and Biological Response Modifiers.

1993 ◽  
Vol 55 (1) ◽  
pp. 43-46
Author(s):  
Jun YOSHIDA ◽  
Juichiro NAKAYAMA ◽  
Nobuyuki SHIMIZU ◽  
Shonosuke NAGAE ◽  
Yoshiaki HORI
Keyword(s):  
Malignant Melanoma ◽  
Biological Response ◽  
Biological Response Modifiers ◽  
Cancer Drugs ◽  
Anti Cancer

Current Scenario in Structure and Ligand-Based Drug Design on Anti-colon Cancer Drugs

2019 ◽  
Vol 24 (32) ◽  
pp. 3829-3841 ◽  
Author(s):  
Lakshmanan Loganathan ◽  
Karthikeyan Muthusamy
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Anticancer Agent ◽  
Computational Power ◽  
Cancer Drugs ◽  
Recent Advances ◽  
Anti Cancer ◽  
Drug Designing ◽  
Current Scenario ◽  
Molecular Modeling Studies

Worldwide, colorectal cancer takes up the third position in commonly detected cancer and fourth in cancer mortality. Recent progress in molecular modeling studies has led to significant success in drug discovery using structure and ligand-based methods. This study highlights aspects of the anticancer drug design. The structure and ligand-based drug design are discussed to investigate the molecular and quantum mechanics in anti-cancer drugs. Recent advances in anticancer agent identification driven by structural and molecular insights are presented. As a result, the recent advances in the field and the current scenario in drug designing of cancer drugs are discussed. This review provides information on how cancer drugs were formulated and identified using computational power by the drug discovery society.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents

2006 ◽  
Vol 1 (3) ◽  
pp. 327-346 ◽  
Author(s):  
Stephen Ralph ◽  
Pauline Low ◽  
Langfeng Dong ◽  
Alfons Lawen ◽  
Jiri Neuzil
Keyword(s):  
Cancer Drugs ◽  
Anti Cancer ◽  
Patent Documents

Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines

2020 ◽  
Vol 20 (8) ◽  
pp. 1017-1027
Author(s):  
Abdul M. Baig ◽  
Zohaib Rana ◽  
Mohammad M. Mannan ◽  
Areeba Khaleeq ◽  
Fizza Nazim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Drug Efflux ◽  
Adapter Proteins ◽  
Cancer Drugs ◽  
Protein Targets ◽  
Anti Cancer ◽  
Drug Efflux Pumps ◽  
Cancer Agent ◽  
Androgen Independent

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs. Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa). Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines. Results: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects. Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.

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