Apoptosis and G2/M cell cycle arrest induced by a timosaponin A3 from Anemarrhena asphodeloides Bunge on AsPC-1 pancreatic cancer cells.
Phytomedicine
; 56: 48-56, 2019 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-30668353
ABSTRACT
BACKGROUND:
Timosaponin A3 (TA3), one of the active components of spirostanol saponin isolated from A. asphodeloides, is widely used as an anticancer agent in a variety of cancer cell lines. However, the research on the anticancer efficacy is very limited in human pancreatic cancer models.PURPOSE:
In this study, we investigated the molecular targets in the active components of A. asphodeloides, which showed anti-cancer effects in human pancreatic cancer cells, and confirmed the pathways involved. STUDYDESIGN:
The apoptotic effects of five solvent extracts of A. asphodeloides in human pancreatic cancer cells (AsPC-1) was studied, and the phytochemical leading to their effects identified. Next, we determined whether the phytochemical inhibit STAT3 and ERK1/2, and investigated the pathways involved.METHODS:
Five solvent extracts of A. asphodeloides (100⯠µg/ml, 24 â¯h) was investigated for their cytotoxicity against AsPC-1 cells. The active ingredient of the extract exhibiting the highest toxicity were analyzed by liquid chromatography-mass spectrometry. Next, we studied the mechanism of action of the phytochemical in pancreatic cancer. Cell cycle and annexin V/FITC assays were performed to assess cell growth and apoptosis capacity. The effects on apoptosis and proliferation-related pathways, STAT3, and MAPKs were confirmed at the protein level using immunoblotting. The factors regulated in the pathways were investigated using reverse transcription polymerase chain reaction.RESULTS:
The results showed that the ethyl acetate extract of A. asphodeloides (EAA) induced apoptotic and anti-proliferative activities through the STAT3 and MAPKs pathways. We found that TA3, an active component of EAA, inhibits constitutive STAT3 and ERK1/2 proteins. EAA and TA3 decreased the viability of AsPC-1 cells, leading to cell cycle arrest at the sub-G1 and G2/M phases. Moreover, TA3 inhibited the expression of various genes encoding anti-apoptotic (Bcl-2, Bcl-xl), proliferative (Cyclin D1), metastatic (MMP-9), and angiogenic (VEGF-1) proteins.CONCLUSION:
The results indicated that TA3, an active phytochemical from A. asphodeloides, could induce apoptosis and suppress cell proliferation by inhibiting the STAT3 and ERK1/2 pathways. Thus, TA3 is a candidate cancer chemotherapeutic agent instead to treat human pancreatic cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Saponinas
/
Esteroides
/
Anemarrhena
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2019
Tipo de documento:
Article