Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells.
J Pharm Pharmacol
; 66(10): 1394-409, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-25039905
ABSTRACT
OBJECTIVES:
Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells.METHODS:
(2-Hydroxypropyl)-ß-cyclodextrin inclusion complex and solid dispersions (carboxymethyl cellulose, polyvinylpyrrolidone and sodium lauryl sulphate) of KA were prepared. In addition, a salt of KA, potassium koetjapate was synthesized. KEYFINDINGS:
Potassium koetjapate demonstrated higher solubility than the other tested formulations with enhanced cytotoxicity against HCT 116 cells. The enhanced efficacy of potassium koetjapate is attributed to apoptotic induction of nuclear condensation and disruption of mitochondrial membrane potential in the cells. Interestingly, potassium koetjapate was found to be safe in rats after oral administration (LD50 > 2000 mg/kg).CONCLUSIONS:
The salt formulation of KA appears to modulate the capability of the parent compound by enhancing its solubility and improves its bioefficacy against colon cancer cells, suggesting attractive roles for its applications in medicine.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
/
Hidroterapia
Asunto principal:
Potasio
/
Triterpenos
/
Extractos Vegetales
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Neoplasias Colorrectales
/
Meliaceae
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Fitoterapia
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Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pharm Pharmacol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Malasia