Hapalindole H Induces Apoptosis as an Inhibitor of NF-ĸB and Affects the Intrinsic Mitochondrial Pathway in PC-3 Androgen-insensitive Prostate Cancer Cells
Autor: | Jiachen Zi, Shunyan Mo, Jimmy Orjala, Esperanza J. Carcache de Blanco, Ulyana Muñoz Acuña |
---|---|
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Cancer Research Apoptosis Mitochondrion Article Indole Alkaloids 03 medical and health sciences Prostate cancer Western blot Prostate Cell Line Tumor medicine Humans Cytotoxic T cell Membrane Potential Mitochondrial Molecular Structure medicine.diagnostic_test Chemistry NF-kappa B Cancer General Medicine Cell sorting Intercellular Adhesion Molecule-1 medicine.disease Molecular biology Mitochondria Prostatic Neoplasms Castration-Resistant 030104 developmental biology medicine.anatomical_structure Oncology MCF-7 Cells HT29 Cells Signal Transduction |
Zdroj: | Anticancer Research. 38:3299-3307 |
ISSN: | 1791-7530 0250-7005 |
Popis: | BACKGROUND Prostate cancer presents the highest incidence rates among all cancers in men. Hapalindole H (Hap H), isolated from Fischerella muscicola (UTEX strain number LB1829) as part of our natural product anticancer drug discovery program, was found to be significantly active against prostate cancer cells. MATERIALS AND METHODS In this study, Hap H was tested for nuclear factor-kappa B (NF-ĸB) inhibition and selective cytotoxic activity against different cancer cell lines. The apoptotic effect was assessed on PC-3 prostate cancer cells by fluorescence-activated cell sorting analysis. The underlying mechanism that induced apoptosis was studied and the effect of Hap H on mitochondria was evaluated and characterized using western blot and flow cytometric analysis. RESULTS Hap H was identified as a potent NF-ĸB inhibitor (0.76 μM) with selective cytotoxicity against the PC-3 prostate cancer cell line (0.02 μM). The apoptotic effect was studied on PC-3 cells. The results showed that treatment of PC-3 cells with Hap H reduced the formation of NAD(P)H, suggesting that the function of the outer mitochondrial membrane was negatively affected. Thus, the mitochondrial transmembrane potential was assessed in Hap H treated cells. The results showed that the outer mitochondrial membrane was disrupted as an increased amount of JC-1 monomers were detected in treated cells (78.3%) when compared to untreated cells (10.1%), also suggesting that a large number of treated cells went into an apoptotic state. CONCLUSION Hap H was found to have potent NF-ĸB p65-inhibitory activity and induced apoptosis through the intrinsic mitochondrial pathway in hormone-independent PC-3 prostate cancer cells. |
Databáze: | OpenAIRE |
Externí odkaz: |