2-hexyl-4-pentynoic acid, a potential therapeutic for breast carcinoma by influencing RPA2 hyperphosphorylation-mediated DNA repair

Wenwen Ding, David Lim, Zhendong Wang, Zuchao Cai, Guochao Liu, Fengmei Zhang, Zhihui Feng

Research output: Contribution to journalArticlepeer-review

Abstract

Breast carcinoma is one of the most common malignancies in women. Previous studies have reported that 500 μM valproic acid can sensitize breast tumor cells to the anti-neoplastic agent hydroxyurea. However, the dose requirements for valproic acid is highly variable due to the wide inter-individuals clinical characteristics. High therapeutic dose of valproic acid required to induce anti-tumor activity in solid tumor was associated with increased adverse effects. There are attempts to locate suitably high-efficient low-toxicity valproic acid derivatives. We demonstrated that lower dose of 2-hexyl-4-pentynoic acid (HPTA; 15 μM) has similar effects as 500 μM VPA in inhibiting breast cancer cell growth and sensitizing the tumor cells to hydroxyurea on MCF7 cells, EUFA423 cells, MCF7 cells with defective RPA2-p gene and primary culture cells derived from tissue-transformed breast tumor cells. We discovered HPTA resulted in more DNA double-strand breaks, the homologous recombination was inhibited through the interference of the hyperphosphorylation of replication protein A2 and recombinase Rad51. Our data postulate that HPTA may be a potential novel sensitizer to hydroxyurea in the treatment of breast carcinoma.

Original languageEnglish
Article number102940
Number of pages11
JournalDNA Repair
Volume95
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Breast cancer
  • HDACi, histone deacetylase inhibitor
  • HPTA, 2-hexyl-4-pentynoic acid
  • HU, hydroxyurea
  • VPA, valproic acid

Fingerprint Dive into the research topics of '2-hexyl-4-pentynoic acid, a potential therapeutic for breast carcinoma by influencing RPA2 hyperphosphorylation-mediated DNA repair'. Together they form a unique fingerprint.

Cite this