貫葉金絲桃素誘導外在/內在細胞凋亡信號傳導並抑制 NF-кB 抑制前列腺癌細胞的轉移

廖丞晞^1,2,3,4 、張文馨^2,3 、胡佩欣^2,3 、蔡佳紋^2,3 、吳錫金⁵、包大靝^2,3,4

¹國軍臺中總醫院外科部泌尿外科; ²中國醫藥大學生物醫學研究所; ³Terry Fox癌症研究室;

⁴國防醫學院臨床醫學研究所; ⁵中國醫藥大學附設醫院泌尿外科

Hyperforin Induces Extrinsic/Intrinsic Apoptosis Signaling and Inhibits NF-кB for Metastasis Suppression in Prostate Cancer Cells

Cheng-Hsi Liao^1,2,3,4 , Wen-Shin Chang^2,3 , Pei-Shin Hu^2,3, Chia-Wen Tsai^2,3, Hsi-Chin Wu⁵,and Da-Tian Bau^1,2

¹ Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.; ² Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.; ³ Terry Fox Cancer Research Laboratory; ⁴ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.;

⁵ Department of Urology, China Medical University Hospital, Taichung, Taiwan, R.O.C.;

Purpose: Prostate cancer is the second most prevalent cancer for men and the fifth leading cause of death in the world. According to the most updated statistical survey, up to 1,276,106 newly diagnosed prostate cancer cases were reported worldwide, with relatively high prevalence in the developed countries. It is urgently needed to figure out novel and practical anti-prostate cancer drugs. In this study, we have some data showing that hyperforin can be the potential one. In order to examine the effects and mechanisms of hyperforin on prostate cancer cells, PC-3 cells together with other prostate cancer cells such as LNCaP cells, will be subject to the treatments of hyperforin with various dosage and duration.    

Materials and Methods: The alterations in cell viability, production of reactive oxygen species (ROS), and pro- and anti-apoptotic signaling will be measured via typical MTT assay, flow cytometry, ELISA and Western blot analyzing modules. Specifically, the effects of hyperforin on the expression of nuclear factor-kappaB (NF-кB) p65 (Ser276), tumor progression-associated proteins, as well as on cell invasion will be followed and measured via Western blotting, cell invasion and migration assay modules, respectively.

Results: Our results show that hyperforin significantly induces apoptosis, extrinsic/intrinsic apoptotic signaling, accumulation of cytosol ROS, and calcium signaling. In addition, hyperforin can significantly diminish the expression of NF-кB p65 (Ser276), anti-apoptotic and tumor progression-associated proteins, as well as the cell invasion ability of PC-3 cells. Putting these highlight findings together, our pilot results demonstrate that hyperforin may trigger the cell apoptosis via both extrinsic and intrinsic apoptosis machineries and suppresses the NF-кB-mediated invasive capacities of PC-3 cells.

Conclusions: All our finding may of academic value in revealing the intracellular signaling network triggered by hyperforin in prostate cancer cells, and simultaneously of clinical value in providing a potential natural compound for practice in prostate cancer therapy.