SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo

被引:3
|
作者
Park, Ji Eon [1 ]
Shin, Woo-Cheol [2 ]
Lee, Hyo-Jung [1 ]
Yoon, Dahye [2 ]
Sim, Deok Yong [1 ]
Ahn, Chi-Hoon [1 ]
Park, Su-Yeon [1 ]
Shim, Bum Sang [1 ]
Park, So Jung [3 ]
Kim, Kyung Seok [3 ]
Park, Geum Duck [3 ]
Kim, Sung-Hoon [1 ]
Lee, Dae Young [2 ]
机构
[1] Kyung Hee Univ, Coll Korean Med, 26 Kyungheedae Ro, Seoul 02447, South Korea
[2] RDA, Dept Herbal Crop Res, Natl Inst Hort & Herbal Sci, Eumseong 27709, South Korea
[3] Suheung Res Ctr, Seongnam, South Korea
关键词
apoptosis; benign ptatic hyperplasia; FOXO3a; ros; ROS; SH-PRO; ANDROGEN-RECEPTOR; CANCER CELLS; DOWN-REGULATION; APOPTOSIS; PATHWAY; FOXO3A; PSA;
D O I
10.1002/ptr.7626
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.
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收藏
页码:452 / 463
页数:12
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