Anti-migration and anti-invasion effects of 2-hydroxy-6-tridecylbenzoic acid is associated with the enhancement of CYP1B1 expression through activating the AMPK signaling pathway in triple-negative breast cancer cells

Abstract

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.

Graphical Abstract

Keywords:

• Triple-negative breast cancer
• 2-hydroxy-6-tridecylbenzoic acid
• CYP1B1
• AMPK
• migration
• invasion

Disclosure statement

The authors have declared no conflict of interest.

Additional information

Funding

This work was supported by 10-100-1000 Program for High-End Talents Introduction of Liaoning Province in China [grant number 521082403-880303-88030312004].