Final-2 targeted glycolysis mediated apoptosis and autophagy in human lung adenocarcinoma cells but failed to inhibit xenograft in nude mice.
Food Chem Toxicol
; 130: 1-11, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31054290
ABSTRACT
Natural products derived from fruits have multiple antitumor potential. However, very few have been developed for clinical therapy, due to the limited efficiency or insufficient study of their mechanism. Since lung cancer is the most common cancer in the world, there is still need to explore novel compounds but their molecular mechanisms remain elusive. In this study, a new compound Final-2 was synthesized. Final-2 exhibited antitumor activity in A549â¯cells by promoting apoptosis and blocking autophagy. Moreover, Final-2 significantly induced G0/G1 cycle arrest and inhibited cell malignancy. Intracellular molecular targets investigation showed that Final-2 inhibited the Gluts, which resulted in downregulation of glucose metabolism and the oncogene c-Myc and Kras expression in vitro. However, according the autophagy inhibitor CQ and Kras inhibitors test, low concentration of Final-2 showed some controversial effects. In A549 xenograft mice model, 10â¯mg/kg and 20â¯mg/kg of Final-2 showed no and partial tumor inhibition, respectively. Moreover, a high dose of Final-2 induced serious liver necrosis. Therefore, the results indicated that even though Final-2 was efficient in suppressing the cancer cell growth in vitro, it failed to inhibit tumors in vivo and showed significant liver toxicity, which was its limitation as a potential antitumor drug.
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Texto completo:
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Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
Assunto principal:
Apoptose
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Adenocarcinoma de Pulmão
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Glicólise
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Neoplasias Pulmonares
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Neoplasias Experimentais
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Antineoplásicos Fitogênicos
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China