Hyperforin Induces Apoptosis Through Extrinsic/Intrinsic Pathways and Inhibits NF-ĸB-modulated Survival and Invasion Potential in Bladder Cancer.

Abstract

BACKGROUND/AIM:

Muscle-invasive bladder cancer (MIBC) has long been recognized as a difficult to treat cancer type, thus a new treatment strategy is needed. The major purpose of the present study was to verify the anticancer effect of hyperforin and the mechanism through which it affects tumor cell growth and invasion in bladder cancer in vitro.

MATERIALS AND METHODS:

Bladder cancer TSGH-8301 cells were treated with different concentrations of hyperforin for different durations of time. The changes in cell viability, production of calcium and reactive oxygen species (ROS), and anti-apoptotic signaling were evaluated using MTT assay, flow cytometry, and western blot analysis. The effect of hyperforin on the expression of nuclear factor-kappaB (NF-ĸB) p65 (Ser276), tumor progression-associated proteins, as well as on cell invasion was investigated using western blotting and cell invasion assay, respectively.

RESULTS:

Hyperforin significantly induces apoptosis, extrinsic/intrinsic apoptotic signaling, accumulation of cytosol ROS, and calcium signalling. Hyperforin also significantly diminishes the expression of NF-ĸB p65 (Ser276), anti-apoptotic and tumor progression-associated proteins, as well as the cell invasion ability of TSGH-8301 cells.

CONCLUSION:

Our findings demonstrate that hyperforin triggers apoptosis depending on extrinsic/intrinsic pathways and suppresses NF-ĸB-mediated cell survival as well as the invasive properties of bladder cancer in vitro.

• Authors: Yu-Chang Liu, Kuang-Hsuan Lin, Jung-Hung Hsieh, Jing-Gung Chung, Zhao-Lin Tan, Fei-Ting Hsu, Chih-Hung Chiang
• Journal: In vivo (Athens, Greece) (In Vivo) 2019 Nov-Dec Vol. 33 Issue 6 Pg. 1865-1877 ISSN: 1791-7549 [Electronic] Greece
• PMID: 31662514 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• NF-kappa B
• Reactive Oxygen Species
• Terpenes
• Phloroglucinol
• hyperforin

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Humans
• NF-kappa B (metabolism)
• Neoplasm Invasiveness (pathology)
• Phloroglucinol (analogs & derivatives, pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Terpenes (pharmacology)
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)