Dracocephalum palmatum Stephan extract induces caspase and mitochondriadependent apoptosis via Myc inhibition in diffuse large B cell lymphoma.
Oncol Rep
; 44(6): 2746-2756, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33125144
ABSTRACT
Dracocephalum palmatum Stephan (DPS), a medicinal plant used by Russian nomads, has been known to exhibit antioxidant properties. However, to the best of our knowledge, its anticancer effect has not been elucidated. The present study aimed to evaluate the tumorsuppressive effect of DPS extract (DPSE) in diffuse large B cell lymphoma (DLBCL) and the underlying mechanism. MTS assays and Annexin V staining were performed to assess the antiproliferative and apoptotic effects of DPSE, respectively. To reveal the underlying mechanisms, the levels of pro and antiapoptotic Bcl2 members were analyzed by western blotting. Rescue experiments were performed to investigate the potential involvement of Myc in DPSEinduced tumorinhibitory effects. Additionally, highperformance liquid chromatography analysis was performed to analyze the components with anticancer effects. Exposure of multiple DLBCL cell lines to DPSE significantly decreased cell viability and increased apoptosis, whereas it had no effect on the survival of normal cells in vitro and in vivo. This indicates that its cytotoxic effect may be specific to cancer cells. Mechanistically, cell death induced by DPSE was dependent on the activation of caspase3/7 and the disruption of mitochondrial membrane potential. Treatment with the extract ameliorated the expression of antiapoptotic Bcl2 members BclxL and Mcl1, and upregulated that of proapoptotic Bcl2 members Bax and Bak. These modulations led to the disruption of mitochondrial membrane potential, which culminated in the activation of executioner caspases3 and 7. Notably, overexpression of Myc inhibited DPSEinduced cell killing, indicating the involvement of Myc in this process. Given that dysregulation of Myc is strongly associated with the pathobiology of DLBCL, the present study highlights the potential therapeutic efficacy of DPSE in patients with DLBCL with aberrant Myc expression. Furthermore, fractionation of DPSE by thin layer chromatography and liquid chromatography/mass spectrometrybased investigation of the fraction with bioactive compounds demonstrated that flavonoids may be responsible for most, if not all, of the antilymphoma effect. Efforts to identify the bioactive flavonoids is currently underway.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
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Proteínas Proto-Oncogênicas c-myc
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Linfoma Difuso de Grandes Células B
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Lamiaceae
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Antineoplásicos Fitogênicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article