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Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells
- Source :
- Phytomedicine. 22:946-951
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Introduction Chemotherapy is one of the preferred mode of treatment of malignancies, but is complicated by the expression of diverse resistance mechanisms of cancer cells. Methods In the present study, we investigated the cytotoxicity of five alkaloids including a furoquinoline montrofoline (1) and four acridones namely 1-hydroxy-4-methoxy-10-methylacridone (2), norevoxanthine (3), evoxanthine (4), 1,3-dimethoxy-10-methylacridone (5) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry. Results Furoquinoline 1 as well as the acridone alkaloids 2–5 displayed cytotoxic effects with IC50 values below 138 µM on all the 9 tested cancer cell lines. The IC50 values ranged from 41.56 µM (towards hepatocarinoma HepG2 cells) to 90.66 µM [towards colon carcinoma HCT116 (p53−/−) cells] for 1, from 6.78 µM [towards HCT116 (p53−/−) cells) to 106.47 µM [towards breast adenocarcinoma MDA-MB-231-pcDNA cells] for 2, from 5.72 µM (towards gliobastoma U87MG.ΔEGFR cells) to 137.62 µM (towards leukemia CCRF-CEM cells] for 3, from 6.11 µM [towards HCT116 (p53+/+) cells] to 80.99 µM (towards HepG2 cells] for 4, from 3.38 µM (towards MDA-MB-231-BCRP cells) to 58.10 µM (towards leukemia CEM/ADR5000 cells] for 5 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Acridone alkaloid 5 induced apoptosis in CCRF-CEM leukemia cells, mediated by increased ROS production. Conclusions The five tested alkaloids and mostly acridone 5 are potential cytotoxic natural products that deserve more investigations to develop novel cytotoxic compounds against multifactorial drug-resistant cancers.
- Subjects :
- Pharmaceutical Science
Apoptosis
Pharmacology
Biology
Furoquinoline alkaloid
Flow cytometry
Inhibitory Concentration 50
chemistry.chemical_compound
Alkaloids
Cell Line, Tumor
Drug Discovery
medicine
Humans
Cytotoxic T cell
Cytotoxicity
Membrane Potential, Mitochondrial
Molecular Structure
medicine.diagnostic_test
Cell Cycle
medicine.disease
Antineoplastic Agents, Phytogenic
Molecular biology
Drug Resistance, Multiple
Acridone
Leukemia
Complementary and alternative medicine
chemistry
Drug Resistance, Neoplasm
Caspases
Cancer cell
Molecular Medicine
Reactive Oxygen Species
Acridones
Subjects
Details
- ISSN :
- 09447113
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Phytomedicine
- Accession number :
- edsair.doi.dedup.....7968bb38e01340415c436ae9ab3bd8cc