Genipin Enhances the Therapeutic Effects of Oxaliplatin by Upregulating BIM in Colorectal Cancer.
Mol Cancer Ther
; 18(4): 751-761, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30787174
ABSTRACT
Despite an increase in the survival rate of patients with cancer owing to the use of current chemotherapeutic agents, adverse effects of cancer therapies remain a concern. Combination therapies have been developed to increase efficacy, reduce adverse effects, and overcome drug resistance. Genipin is a natural product derived from Gardenia jasminoides, which has been associated with anti-inflammatory, anti-angiogenic, and anti-proliferative effects; hypertension; and anti-ischemic brain injuries. However, the enhancement of oxaliplatin sensitivity by genipin remains unexplored. Our study showed that a combination of genipin and oxaliplatin exerts synergistic antitumor effects in vitro and in vivo in colorectal cancer cell lines through the reactive oxygen species (ROS)/endoplasmic reticulum (ER) stress/BIM pathway. Importantly, the combination did not affect normal colon cells. BIM knockdown markedly inhibited apoptosis induced by the combination. In addition, genipin induced ROS by inhibiting superoxide dismutase 3 activity. These findings suggest that genipin may be a novel agent for increasing the sensitivity of oxaliplatin against colorectal cancer. The combination of oxaliplatin and genipin hold significant therapeutic potential with minimal adverse effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
/
Neoplasias Colorretais
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Iridoides
/
Oxaliplatina
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2019
Tipo de documento:
Article