Bishydroquinone Renieramycin M Induces Apoptosis of Human Lung Cancer Cells Through a Mitochondria-dependent Pathway.
Anticancer Res
; 36(12): 6327-6333, 2016 12.
Article
en En
| MEDLINE
| ID: mdl-27919953
ABSTRACT
BACKGROUND:
Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells.METHODS:
HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively. The key molecular markers of mitochondrial apoptosis pathway were determined by western blot analysis.RESULTS:
HQ-RM exhibited stronger cytotoxicity than RM. HQ-RM reduced vitality of lung cancer cells in a dose-dependent manner. Nuclear staining assay indicated that apoptotic cell death was the main mechanism of toxicity caused by HQ-RM. Protein analysis revealed that HQ-RM-mediated apoptosis involved the increase of pro-apoptotic B-cell lymphoma 2 associated X (BAX) protein, and the decrease of anti-apoptosis myeloid cell leukemia 1 (MCL1) and B-cell lymphoma 2 (BCL2) proteins. Moreover, caspase-9 and -3 and Poly (ADP-ribose) polymerase (PARP) were dramatically cleaved in response to HQ-RM treatment.CONCLUSION:
HQ-RM has highly potent anticancer activity, greater than its parental RM, and induces lung cancer cell apoptosis through a mitochondrial apoptosis caspase-dependent mechanism. This information benefits the development of this compound for cancer therapy.Palabras clave
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Tetrahidroisoquinolinas
/
Neoplasias Pulmonares
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2016
Tipo del documento:
Article
País de afiliación:
Tailandia