Distinct effects of novel naphtoquinone-based triazoles in human leukaemic cell lines.
J Pharm Pharmacol
; 67(12): 1682-95, 2015 Dec.
Article
in En
| MEDLINE
| ID: mdl-26256440
ABSTRACT
OBJECTIVES:
The aim of this study was to investigate the cytotoxic effect of new 1,4-naphthoquinone- 1,2,3-triazoles, named C2 to C8 triazole derivatives, towards human cancer cell lines.METHODS:
The effect on cell viability was assessed by MTT and propidium iodide assays. The cytotoxic effect of C2 and C3 in K562 and HL-60 cells were analyzed by flow cytometry, DNA fragmentation and reactive oxygen species (ROS) production. Western blot and q-PCR procedures were also performed. KEYFINDINGS:
C2 and C3 inhibited both K562 and HL-60 cells growth in a concentration-dependent manner. C2 presented the highest cytotoxic activity with an IC50 of approximately 14 µm and 41 µm for HL-60 and K562 cells, respectively, while being less toxic to normal peripheral blood monocyte cells. Both derivatives induced cellular changes in HL-60 cells, characteristic of apoptosis, such as mitochondrial membrane depolarization, phosphatidylserine externalization, increasing sub-G1 phase, DNA fragmentation, downregulating Bcl-2 protein and upregulating Bax protein. In K562 cells, C2 and C3 induced S-phase arrest of cell cycle, which was associated with upregulation of p21. The effect of these derivatives in HL-60 cells can be related to the ROS intracellular level.CONCLUSION:
Taken together our results showed that C2 and C3 triazole derivatives presented the best potential for drug design.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triazoles
/
Leukemia
/
Naphthoquinones
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
J Pharm Pharmacol
Year:
2015
Document type:
Article
Affiliation country: