Anticancer Drug Metabolism: Chemotherapy Resistance and New Therapeutic Approaches

Akhdar, Hanane; Legendre, Claire; Aninat, Caroline; More, Fabrice

doi:10.5772/30015

Cited by 30 publications

(23 citation statements)

References 205 publications

(197 reference statements)

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“…The absence or reduction of Form II plasmid DNA specified a remarkable safeguard offered by the extracts. Most of the anticancer drugs work either by reducing the free radicals or through direct interaction with the DNA (Akhdar et al, 2012). This study clearly implies the protection of DNA by these extracts.…”

Section: Discussionmentioning

confidence: 65%

Bioactive potential of endophyticMyrotheciumsp. isolate M1-CA-102, associated withCalophyllum apetalum

Karmakar

Sunil

Prakash

2014

Pharmaceutical Biology

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Context: Endophytes colonizing medicinal plants are diverse, constituting a rich bioresource for novel natural products. Objective: Myrothecium sp. isolate M1-CA-102 was the most promising among the 16 Myrothecium isolates screened. The bioactive potential of the crude extract from the Calophyllum apetalum Willd. endophytic Myrothecium sp. (Alb. & Schwein.) Ditmar (Incertae sedis) isolate M1-CA-102 and its thin layer chromatography (TLC) fractions were screened based on antioxidant, anti-inflammatory, antimicrobial activities, and cytotoxicity. Materials and methods: The antioxidant activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 0 -azinobis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical scavenging capacities. Further, 15-lipoxygenase (15-LOX) and human cyclooxygenase-2 (COX-2) inhibition were assessed at different concentrations (25, 50, and 100 mg/mL for the crude extract, 5, 25, and 50 mg/mL for the TLC fractions). DNA-nicking assay as an indicator of the capacity of extracts to scavenge hydroxyl radical was recorded at a concentration of 50 mg/mL. Cell cytotoxicity was recorded by colorimetric 3-(4,5-dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antibacterial (Bacillus subtilis) and antiCandida (Candida albicans) assays were performed by the microdilution method. Results: The DPPH and ABTS IC 50 values of M1-CA-102 extract were 10 and 6 mg/mL compared with 6.1 and 7.03 mg/mL for the positive control quercetin. The cytotoxicity IC 50 value of M1-CA-102 extract was 37 mg/mL, while the M-I TLC fraction was 21 mg/mL. The M1-CA-102 extract gave an IC 50 value of 58 and 8 mg/mL for 15-LOX and COX-2, respectively. The MIC values for antimicrobial activity for M1-CA-102 extract ranged from 35 to 54 mg/mL, while for the TLC fractions, it ranged from 91 to 515 mg/mL. Conclusion:The results indicate that Myrothecium M1-CA-102 isolated from C. apetalum is a potential source of natural metabolites of pharmaceutical importance.

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Section: Discussionmentioning

confidence: 65%

Bioactive potential of endophyticMyrotheciumsp. isolate M1-CA-102, associated withCalophyllum apetalum

Karmakar

Sunil

Prakash

2014

Pharmaceutical Biology

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“…Resistance to chemotherapy is a major hurdle limiting the efficacy of MM treatment. Anticancer drugs resistance can be innate –primary- or acquired over time following exposure to the drug and involves diverse molecular mechanisms, in particular, altered local drug metabolism and detoxification process is a major barrier that lies between chemotherapeutic agents and their intended curative potential [4,5]. …”

Section: Introductionmentioning

confidence: 99%

Drug metabolism and clearance system in tumor cells of patients with multiple myeloma

et al. 2014

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Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival. MMCs of patients with a favourable outcome have an increased expression of genes coding for xenobiotic receptors (RXRα, LXR, CAR and FXR) and accordingly of their gene targets, influx transporters and phase I/II DMEs. On the contrary, MMCs of patients with unfavourable outcome displayed a global down regulation of genes coding for xenobiotic receptors and the downstream detoxification genes but had a high expression of genes coding for ARNT and Nrf2 pathways and ABC transporters. Altogether, these data suggests ARNT and Nrf2 pathways could be involved in MM primary resistance and that targeting RXRα, PXR, LXR and FXR through agonists could open new perspectives to alleviate or reverse MM drug resistance.

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“…Nowadays, it was known 11 human OATPs, and their amino acid sequences were conventionally divided into 6 groups [7, 21,101,106]. OATP amino acid sequences are expressing in certain schemes in healthy cells, tissues, organs, resident endothelial cells and other biological barriers, but in pathological sites, they will be overexpression and may contravene their amino acid sequences and also differ from the OATP amino acid sequences in normal cells and tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Multidrug resistance induced by drugs at an early administration, the cells can then develop cross-resistance to several unexposed and structurally unrelated chemotherapeutic agents. The mechanisms of multidrug resistance are: reducing the absorption of therapeutic substances, changes in cellular metabolic pathways and increasing the outflow of active therapeutic substances from the cells [89,[100][101][102][103]. Overexpression of ATP-binding cassette (ABC) transporter is a common reason for the appearance of MDR in the tumors.…”

Section: Introductionmentioning

confidence: 99%

Systems for the delivery of chemotherapeutic drugs, new approaches and perspective

Jeewantha¹

2017

Russ Open Med J

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Great perspectives in the field of drug therapy are currently associated with the targeted delivery of drugs to the organ, tissue or cells. Drug delivery systems (DDS) play a key role in enhancing the quality of chemotherapy in cancer disease. The intense interest in the topic of chemotherapy is the development of novel methods of drug delivery. The success of anti-tumor chemotherapy significantly dependends on the ability of therapeutic substances to achieve its target as well as minimal accumulation in non-specific sites (healthy organs and tissues). According to that, splendid perspectives in the field of chemotherapy are currently associated with the targeted delivery of drugs to the organs, tissues or cells. The essence of targeted delivery is that the drug itself, but more often a means of delivery systems (the vector, containers, and others.) modified by molecules, which can be identified by a unique receptor on cells or target sites. Then they are called "targeted drug delivery systems". At the same time, the engineering of multifunctional nanocarriers with several useful properties in one carrier (nanoparticles, liposomes, micelles, dendrimers, and others.) can significantly enhance the efficacy of many therapeutic and diagnostic protocols. In this article, summarize the accumulated information about potential possibilities of DDS, and the practical applications in cancer chemotherapy.

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Anticancer Drug Metabolism: Chemotherapy Resistance and New Therapeutic Approaches

Cited by 30 publications

References 205 publications

Bioactive potential of endophyticMyrotheciumsp. isolate M1-CA-102, associated withCalophyllum apetalum

Bioactive potential of endophyticMyrotheciumsp. isolate M1-CA-102, associated withCalophyllum apetalum

Drug metabolism and clearance system in tumor cells of patients with multiple myeloma

Systems for the delivery of chemotherapeutic drugs, new approaches and perspective

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