Corchorusoside C (1), isolated from Streptocaulon juventas collected in Vietnam, was found to be non-toxic 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 (IC 50 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 (IC 50 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 posttreatment 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 non-differential 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.

Background/Aim: Effect of capsicodendrin on the NF-ĸB pathway was studied in MCF-7 cancer cells. Materials and Methods: The transcription factor assay was used to screen for NF-ĸB activity. The effect on IKKβ, ICAM-1, and caspase-7 were studied using western blot. Caspase-1 was studied using Promega Caspase-Glo ® assay. Reactive oxygen species (ROS) were detected using the fluorescent probe DCFH-DA. The potentiometric dye JC-1 was used to assess mitochondrial membrane potential (ΔΨm) and the cell cycle was examined using a fluorescence-activated cell sorter. Results: NF-ĸB p65 inhibitory effect was IC 50 =8.6 μM and cytotoxic activity was IC 50 =7.5 μM. The upstream IKK and the downstream ICAM-1 were down-regulated. Sub G 1 -phase population increased to 81% after 12 h of treatment with capsicodendrin (10 μM) and there was no loss of ΔΨM. Conclusion: Increased levels of intracellular ROS promoted activity of caspase-1 and induced cell death in MCF-7 cells. Capsicodendrin may be a future anticancer agent that prevents the progression of metastatic breast cancer.Despite new effective anticancer treatments, chemoresistant breast tumor cells spread to other organs and the survival rate (26%) remains low for metastatic breast cancer (1-3). Breast cancer patients have high serum levels of proinflammatory cytokine tumor necrosis factor-α (TNF-α). It Materials and MethodsCell culture. The MCF-7 cancer cell line was obtained from American Type Culture Collection (ATCC# HTB-22, Manassas, VA, USA). Cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and Roswell Park Memorial Institute medium (RPMI-1640), containing 10% fetal bovine calf serum and 10% Antibiotic-Antimycotic (Gibco, Rockville, MD, USA). Cells were kept at 37˚C and in an atmosphere containing 5% CO 2 .

The present study aims to continue the study of corchorusoside C (1), a cardenolide isolated from Streptocaulon juventas, as a potential anticancer agent. A mechanistic study was pursued in a zebrafish model and in DU-145 prostate cancer cells to investigate the selectivity of 1 towards NF-κB and PARP-1 pathway elements. Compound 1 was found to inhibit the expression of IKKα and NF-κB p65 in TNF-α induced zebrafish and inhibit the expression of NIK in vitro. The protein expression levels of XRCC-1 were increased and p53 decreased in DU-145 cells. XIAP protein expression was initially decreased after treatment with 1, followed by an increase in expression at doses higher than the IC50 value. The activity of caspase-1 and the protein expression levels of IL-18 were both decreased following treatment of 1. The binding interactions for 1 to NIK, XRCC-1, p53, XIAP, and caspase-1 proteins were explored in molecular docking studies. Additionally, the toxicity profile of 1 in zebrafish was favorable in comparison to its analog digoxin and other anticancer drugs at the same MTD in zebrafish. Overall, 1 targets the noncanconical NF-κB pathway in vivo and in vitro, and is well tolerated in zebrafish supporting its potential in the treatment of prostate cancer.