Repurposing antitubercular agent isoniazid for treatment of prostate cancer.
Biomater Sci
; 7(1): 296-306, 2018 Dec 18.
Article
en En
| MEDLINE
| ID: mdl-30468220
ABSTRACT
The development of versatile antitumor agents with tumor-imaging, targeting and therapeutic activity is promising for clinical cancer therapy. Prostate cancer is still the one of the leading threats to males. Current therapies have restricted clinical efficiency for patients with advanced and metastatic prostate cancer. Recent studies demonstrate that monoamine oxidase A (MAOA) levels elevate with prostate cancer aggression and metastasis. In addition, MAOA inhibitor therapies have been reported as an effective means to reduce the metastasis of prostate cancer and extend mouse survival. Thus, these findings provide evidence that MAOA is promising for the treatment of metastatic and advanced prostate cancer. Herein, three isoniazid (INH)-dye conjugates were synthesized by conjugating MAOA inhibitor INH with mitochondria-targeting NIRF heptamethine dyes to improve the therapeutic efficacy of prostate cancer. These INH-dye conjugates could accumulate in PC-3 cellular mitochondria via organic anion transport peptide (OATP), increase ROS generation, and induce cancer cells apoptosis. In prostate cancer bearing xenografts, INH-dye conjugates showed significantly improved tumor-homing characteristics, resulting in potent antitumor activity via a reduction in MAOA activity. These results suggest that INH-dye conjugates have great potential to be used as versatile antitumor agents with prostate cancer targeting, NIR imaging, and potent antitumor efficacy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Isoniazida
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Inhibidores de la Monoaminooxidasa
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Antituberculosos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biomater Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
China