Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer

Hsin Chih Yeh; Chia Cheng Su; Yen Hsuan Wu; Cheng Hsueh Lee; Bo Ying Bao; Wei Chung Cheng; Shu Chi Wang; Po Len Liu; Chien Chih Chiu; Chih Pin Chuu; Chien Chih Ke; Hsin En Wu; Yuan Ru Chen; Wei Ju Chung; Shu Pin Huang; Chia Yang Li

doi:10.1016/j.ejphar.2022.174929

Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer

Hsin Chih Yeh, Chia Cheng Su, Yen Hsuan Wu, Cheng Hsueh Lee, Bo Ying Bao, Wei Chung Cheng, Shu Chi Wang, Po Len Liu, Chien Chih Chiu, Chih Pin Chuu, Chien Chih Ke, Hsin En Wu, Yuan Ru Chen, Wei Ju Chung, Shu Pin Huang, Chia Yang Li

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

3-bromopyruvic acid (3-BP), a small molecule alkylating agent, has been emerged as a glycolytic inhibitor with anticancer activities. However, the effects of 3-BP on the growth and metastasis in prostate cancer have not been well investigated. Here we investigated the anti-cancer effects of 3-BP on prostate cancer in vitro and in vivo. Cell growth, apoptosis, migration, motility, and invasion were examined. The tumor growth ability was determined using a xenograft murine model. Transcriptome analysis using RNA-seq was performed to explore the mechanism of action of 3-BP. Our experimental results showed that 3-BP effectively inhibits prostate cancer cell growth, especially in castration-resistant prostate cancer (CRPC) cells. Moreover, 3-BP induces apoptosis and suppresses cell migration, motility, epithelial-mesenchymal transition (EMT), and invasion in CRPC cells. In addition, 3-BP also attenuates tumor growth in a xenograft murine model. Through transcriptome analysis using RNA-seq, 3-BP significantly regulates the cell cycle pathway and decreases the expression of downstream cycle cycle-associated genes in CRPC cells. The results of cell cycle analysis indicated that 3-BP arrests cell cycle progression at G2/M in CRPC cells. These results suggest that 3-BP has the potential in inhibiting CRPC progression and might be a promising drug for CRPC treatment.

Original language	English (US)
Article number	174929
Journal	European Journal of Pharmacology
Volume	923
DOIs	https://doi.org/10.1016/j.ejphar.2022.174929
State	Published - May 15 2022
Externally published	Yes

Keywords

3-Bromopyruvic acid
Anticancer
Cell metastasis
Prostate cancer
Transcriptome analysis

ASJC Scopus subject areas

Pharmacology

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10.1016/j.ejphar.2022.174929

Cite this

Yeh, H. C., Su, C. C., Wu, Y. H., Lee, C. H., Bao, B. Y., Cheng, W. C., Wang, S. C., Liu, P. L., Chiu, C. C., Chuu, C. P., Ke, C. C., Wu, H. E., Chen, Y. R., Chung, W. J., Huang, S. P., & Li, C. Y. (2022). Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer. European Journal of Pharmacology, 923, Article 174929. https://doi.org/10.1016/j.ejphar.2022.174929

@article{a980f8b994274f9ea9f421e64c0de510,

title = "Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer",

abstract = "3-bromopyruvic acid (3-BP), a small molecule alkylating agent, has been emerged as a glycolytic inhibitor with anticancer activities. However, the effects of 3-BP on the growth and metastasis in prostate cancer have not been well investigated. Here we investigated the anti-cancer effects of 3-BP on prostate cancer in vitro and in vivo. Cell growth, apoptosis, migration, motility, and invasion were examined. The tumor growth ability was determined using a xenograft murine model. Transcriptome analysis using RNA-seq was performed to explore the mechanism of action of 3-BP. Our experimental results showed that 3-BP effectively inhibits prostate cancer cell growth, especially in castration-resistant prostate cancer (CRPC) cells. Moreover, 3-BP induces apoptosis and suppresses cell migration, motility, epithelial-mesenchymal transition (EMT), and invasion in CRPC cells. In addition, 3-BP also attenuates tumor growth in a xenograft murine model. Through transcriptome analysis using RNA-seq, 3-BP significantly regulates the cell cycle pathway and decreases the expression of downstream cycle cycle-associated genes in CRPC cells. The results of cell cycle analysis indicated that 3-BP arrests cell cycle progression at G2/M in CRPC cells. These results suggest that 3-BP has the potential in inhibiting CRPC progression and might be a promising drug for CRPC treatment.",

keywords = "3-Bromopyruvic acid, Anticancer, Cell metastasis, Prostate cancer, Transcriptome analysis",

author = "Yeh, {Hsin Chih} and Su, {Chia Cheng} and Wu, {Yen Hsuan} and Lee, {Cheng Hsueh} and Bao, {Bo Ying} and Cheng, {Wei Chung} and Wang, {Shu Chi} and Liu, {Po Len} and Chiu, {Chien Chih} and Chuu, {Chih Pin} and Ke, {Chien Chih} and Wu, {Hsin En} and Chen, {Yuan Ru} and Chung, {Wei Ju} and Huang, {Shu Pin} and Li, {Chia Yang}",

note = "Funding Information: This study was supported by grants from the Ministry of Science and Technology, Taiwan, R.O.C. (grant No. MOST 108-2314-B-037-079-MY3 , MOST 109-2622-E-039-004-CC2 , MOST 109-2628-E-039-001-MY3 , MOST 109-2327-B-039-002 and MOST 109-2320-B-037-007-MY3 ), Kaohsiung Medical University (Grant No. NHRIKMU-111-I002 and KMU-DK(A)111003 ), Kaohsiung Medical University Chung-Ho Memorial Hospital (grant No. KMUH105-5M55 ), Taiwan, R.O.C., and China Medical University, Taiwan, R.O.C. (grant No. CMU107-S-24 , CMU108-Z-02 , CMU108-S-22 , CMU109-MF-61 and CMU110-MF-64 ). Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = may,

day = "15",

doi = "10.1016/j.ejphar.2022.174929",

language = "English (US)",

volume = "923",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier",

}

TY - JOUR

T1 - Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer

AU - Yeh, Hsin Chih

AU - Su, Chia Cheng

AU - Wu, Yen Hsuan

AU - Lee, Cheng Hsueh

AU - Bao, Bo Ying

AU - Cheng, Wei Chung

AU - Wang, Shu Chi

AU - Liu, Po Len

AU - Chiu, Chien Chih

AU - Chuu, Chih Pin

AU - Ke, Chien Chih

AU - Wu, Hsin En

AU - Chen, Yuan Ru

AU - Chung, Wei Ju

AU - Huang, Shu Pin

AU - Li, Chia Yang

N1 - Funding Information: This study was supported by grants from the Ministry of Science and Technology, Taiwan, R.O.C. (grant No. MOST 108-2314-B-037-079-MY3 , MOST 109-2622-E-039-004-CC2 , MOST 109-2628-E-039-001-MY3 , MOST 109-2327-B-039-002 and MOST 109-2320-B-037-007-MY3 ), Kaohsiung Medical University (Grant No. NHRIKMU-111-I002 and KMU-DK(A)111003 ), Kaohsiung Medical University Chung-Ho Memorial Hospital (grant No. KMUH105-5M55 ), Taiwan, R.O.C., and China Medical University, Taiwan, R.O.C. (grant No. CMU107-S-24 , CMU108-Z-02 , CMU108-S-22 , CMU109-MF-61 and CMU110-MF-64 ). Publisher Copyright: © 2022

PY - 2022/5/15

Y1 - 2022/5/15

N2 - 3-bromopyruvic acid (3-BP), a small molecule alkylating agent, has been emerged as a glycolytic inhibitor with anticancer activities. However, the effects of 3-BP on the growth and metastasis in prostate cancer have not been well investigated. Here we investigated the anti-cancer effects of 3-BP on prostate cancer in vitro and in vivo. Cell growth, apoptosis, migration, motility, and invasion were examined. The tumor growth ability was determined using a xenograft murine model. Transcriptome analysis using RNA-seq was performed to explore the mechanism of action of 3-BP. Our experimental results showed that 3-BP effectively inhibits prostate cancer cell growth, especially in castration-resistant prostate cancer (CRPC) cells. Moreover, 3-BP induces apoptosis and suppresses cell migration, motility, epithelial-mesenchymal transition (EMT), and invasion in CRPC cells. In addition, 3-BP also attenuates tumor growth in a xenograft murine model. Through transcriptome analysis using RNA-seq, 3-BP significantly regulates the cell cycle pathway and decreases the expression of downstream cycle cycle-associated genes in CRPC cells. The results of cell cycle analysis indicated that 3-BP arrests cell cycle progression at G2/M in CRPC cells. These results suggest that 3-BP has the potential in inhibiting CRPC progression and might be a promising drug for CRPC treatment.

AB - 3-bromopyruvic acid (3-BP), a small molecule alkylating agent, has been emerged as a glycolytic inhibitor with anticancer activities. However, the effects of 3-BP on the growth and metastasis in prostate cancer have not been well investigated. Here we investigated the anti-cancer effects of 3-BP on prostate cancer in vitro and in vivo. Cell growth, apoptosis, migration, motility, and invasion were examined. The tumor growth ability was determined using a xenograft murine model. Transcriptome analysis using RNA-seq was performed to explore the mechanism of action of 3-BP. Our experimental results showed that 3-BP effectively inhibits prostate cancer cell growth, especially in castration-resistant prostate cancer (CRPC) cells. Moreover, 3-BP induces apoptosis and suppresses cell migration, motility, epithelial-mesenchymal transition (EMT), and invasion in CRPC cells. In addition, 3-BP also attenuates tumor growth in a xenograft murine model. Through transcriptome analysis using RNA-seq, 3-BP significantly regulates the cell cycle pathway and decreases the expression of downstream cycle cycle-associated genes in CRPC cells. The results of cell cycle analysis indicated that 3-BP arrests cell cycle progression at G2/M in CRPC cells. These results suggest that 3-BP has the potential in inhibiting CRPC progression and might be a promising drug for CRPC treatment.

KW - 3-Bromopyruvic acid

KW - Anticancer

KW - Cell metastasis

KW - Prostate cancer

KW - Transcriptome analysis

UR - http://www.scopus.com/inward/record.url?scp=85127335871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127335871&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2022.174929

DO - 10.1016/j.ejphar.2022.174929

M3 - Article

C2 - 35364071

AN - SCOPUS:85127335871

SN - 0014-2999

VL - 923

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

M1 - 174929

ER -

Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer

Abstract

Keywords

ASJC Scopus subject areas

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