Oncology reports, 2018-02, Vol.39 (2), p.871-879
2018
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06
- Ist Teil von
- Oncology reports, 2018-02, Vol.39 (2), p.871-879
- Ort / Verlag
- Greece: Spandidos Publications
- Erscheinungsjahr
- 2018
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM‑06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 µmol/l ZBH-ZM-06 was 12.5%, compared to 96.5% for carbonyl-oxycamptothecin (CPT-11). In a chemical stability assay, only 4.9% of ZBH-ZM-06 remained after 4 h at pH 7.4. In addition, 10 µmol/l ZBH-ZM-06 significantly inhibited the tumor cell viability of nine tumor cell lines, compared to CPT-11 and the CPT active ingredient, 7-ethyl-10-hydroxy-camptothecin (SN38) (p<0.01-0.05). In the apoptosis assay, ZBH-ZM-06 increased the ratio of annexin V+/propidium iodide (PI)-/+ cells by flow cytometric analysis (p<0.05). Moreover, ZBH-ZM-06 activated caspase-3 and poly(ADP-ribose)polymerase (PARP) expression by immunoblotting. Furthermore, ZBH-ZM-06 induced a greater G2/M phase arrest ratio, compared to CPT-11 and SN38. These results indicated that ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its: i) release of the effective ingredient; ii) growth inhibition of a broad spectrum of tumor cells; iii) inhibition of DNA topoisomerase (Topo-1); and iv) promotion of apoptosis through an intrinsic signaling pathway. Thus, ZBH-ZM-06 may be applied in the preclinic study for cancer treatment.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1021-335XeISSN: 1791-2431DOI: 10.3892/or.2017.6143Titel-ID: cdi_proquest_journals_1990445667
- Format
- –
- Schlagworte
- Acetylcholinesterase - metabolism, Amino acids, Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - chemistry, Antineoplastic Agents - pharmacology, Apoptosis, Camptothecin - analogs & derivatives, Camptothecin - chemical synthesis, Camptothecin - chemistry, Camptothecin - pharmacology, Cancer research, Cancer therapies, Cancer treatment, Caspase 3 - metabolism, Cell cycle, Cell Cycle - drug effects, Cell Line, Tumor, Cell Survival - drug effects, Cytotoxicity, Deoxyribonucleic acid, DNA, Dose-Response Relationship, Drug, FDA approval, Gene Expression Regulation, Neoplastic - drug effects, Genetic testing, GPI-Linked Proteins - metabolism, Health aspects, Humans, Kinases, Leukemia, Lung cancer, Neoplasms - drug therapy, Neoplasms - metabolism, Ovarian cancer, Poly(ADP-ribose) Polymerases - metabolism, Prodrugs, Prodrugs - chemical synthesis, Prodrugs - chemistry, Prodrugs - pharmacology, Quinolines, Structure-activity relationships (Pharmacology), Testing, Toxicology