Valeric acid acts as a novel HDAC3 inhibitor against prostate cancer

Rui Han; Hongxing Yang; Ya Li; Changquan Ling; Lingeng Lu

doi:10.1007/s12032-022-01814-9

Valeric acid acts as a novel HDAC3 inhibitor against prostate cancer

Med Oncol. 2022 Sep 29;39(12):213. doi: 10.1007/s12032-022-01814-9.

Authors

Rui Han^{1

2

3

4

5

6}, Hongxing Yang^{7

8}, Ya Li⁹, Changquan Ling^{10

11}, Lingeng Lu^{12

13

14}

Affiliations

¹ Department of Chinese Medicine, Naval Medical University, Shanghai, 200433, People's Republic of China. dianxiqiao@foxmail.com.
² Department of Chinese Medicine Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, People's Republic of China. dianxiqiao@foxmail.com.
³ Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, People's Republic of China. dianxiqiao@foxmail.com.
⁴ Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. dianxiqiao@foxmail.com.
⁵ School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. dianxiqiao@foxmail.com.
⁶ Yale Cancer Center, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. dianxiqiao@foxmail.com.
⁷ Beijing University of Traditional Chinese Medicine, Beijing, 100700, People's Republic of China.
⁸ Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, People's Republic of China.
⁹ Department of Integrated Chinese and Western Medicine & Geriatric Oncology, Peking University Cancer Hospital, Beijing, 100142, People's Republic of China.
¹⁰ Department of Chinese Medicine, Naval Medical University, Shanghai, 200433, People's Republic of China.
¹¹ Department of Chinese Medicine Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, People's Republic of China.
¹² Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. lingeng.lu@yale.edu.
¹³ School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. lingeng.lu@yale.edu.
¹⁴ Yale Cancer Center, Yale University, 60 College Street, New Haven, CT, 06520-8034, USA. lingeng.lu@yale.edu.

Abstract

Prostate cancer is the second cause of cancer-related deaths in men worldwide, and new agents for curing the disease are still needed. In this study, we theoretically and experimentally demonstrated that valeric acid (VA) was a HDAC inhibitor, and anti-cancer efficacy of VA in prostate cancer cells was also observed using either 2D or 3D culture systems. VA was cytotoxic for prostate cancer cells but low toxic to normal cells. VA significantly inhibited E2F1/E2F3 expression but increased CASP3 activity. In vivo mouse models further showed its anti-cancer activity and potential property of chemosensitizer with promoting apoptosis. The findings suggest that VA acts as a HDAC3 inhibitor with anti-cancer effect on prostate cancer by regulating E2F1/E2F3/CASP3 axis.

Keywords: Apoptosis; Cancer stemness; HDAC inhibitor; Prostate cancer; Valeric acid.

MeSH terms

Animals
Caspase 3
Histone Deacetylase Inhibitors* / pharmacology
Histone Deacetylases / metabolism
Humans
Male
Mice
Pentanoic Acids
Prostate
Prostatic Neoplasms* / drug therapy

Substances

Histone Deacetylase Inhibitors
Pentanoic Acids
Caspase 3
Histone Deacetylases
histone deacetylase 3
n-pentanoic acid

Grants and funding

202102021125/Guangzhou Municipal Science and Technology Project