A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft.
Nutrition
; 72: 110659, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-31986320
ABSTRACT
OBJECTIVES:
Chemotherapy is one of the major treatments of cancer. However, the emergence of resistance to chemotherapeutic agents is still a major obstacle in the successful management of resistant tumors. Therefore, development of new mechanisms to overcome drug resistance is essential and may be further developed into effective therapies that can flip the switch from drug resistance to susceptibility. The aim of this study was to evaluate a combination consisting of a ketogenic diet and melatonin to determine whether it would inhibit cisplatin- and vincristine-resistant breast cancer.METHODS:
In the in vitro part of the study, drug-resistant cell lines were treated with melatonin and real-time polymerase chain reaction was used to measure levels of gene expression involved in apoptosis and resistance. On the protein level, the activity of caspase-3 and the level of vascular endothelin growth factor protein were determined. In the in vivo part, tumor-bearing mice received one of the following treatments ketogenic diet, melatonin, combination of melatonin and ketogenic diet, vehicle, or chemotherapy.RESULTS:
Successful inhibition of resistant cell lines was achieved by melatonin. This inhibition was mediated by induction of apoptosis, inhibition of angiogenesis, and downregulation of resistance genes. A synergistic anticancer effect was observed between melatonin and the ketogenic diet against resistant breast tumors inoculated in mice with a cure rate of 70%.CONCLUSIONS:
The combination of melatonin and a ketogenic diet represents a promising option to overcome drug resistance in cancer chemotherapy. However, further testing on the protein level using flow cytometry is important to better understand the mechanisms of action.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vincristina
/
Neoplasias de la Mama
/
Cisplatino
/
Resistencia a Antineoplásicos
/
Dieta Cetogénica
/
Melatonina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nutrition
Asunto de la revista:
CIENCIAS DA NUTRICAO
Año:
2020
Tipo del documento:
Article