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Journal of Natural Products 2019-Jun

Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas.

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Gerardo Anaya-Eugenio
Ermias Addo
Nathan Ezzone
Joshua Henkin
Tran Ninh
Yulin Ren
Djaja Soejarto
A Kinghorn
Esperanza de Blanco

Keywords

Abstract

Corchorusoside C (1), isolated from Streptocaulon juventas collected in Vietnam, was found to be nontoxic in a zebrafish ( Danio rerio) model and to induce cytotoxicity in several cancer cell lines with notable selective activity against prostate DU-145 cancer cells (IC50 0.08 μM). Moreover, corchorusoside C induced DU-145 cell shrinkage and cell detachment. In CCD-112CoN colon normal cells, 1 showed significantly reduced cytotoxic activity (IC50 2.3 μM). A preliminary mechanistic study indicated that 1 inhibits activity and protein expression of NF-κB (p50 and p65), IKK (α and β), and ICAM-1 in DU-145 cells. ROS concentrations increased at 5 h post-treatment, and MTP decreased in a dose-dependent manner. Moreover, decreased protein expression of Bcl-2 and increased expression of PARP-1 was observed. Furthermore, corchorusoside C increased both the activity and protein levels of caspases 3 and 7. Additionally, 1 induced sub-G1 population increase of DU-145 cells and modulated caspases in zebrafish with nondifferential morphological effects. Therefore, corchorusoside C (1) induces apoptosis in DU-145 cells and targets the same pathways both in vitro and in vivo in zebrafish. Thus, the use of zebrafish assays seems worthy of wider application than is currently employed for the evaluation of potential anticancer agents of natural origin.

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