Antiproliferative effect of 2-Hydroxy-6-tridecylbenzoic acid from ginkgo biloba sarcotestas through the aryl hydrocarbon receptor pathway in triple-negative breast cancer cells.

Abstract

This study aims to isolate the potential antiproliferative and cytotoxic compounds from ginkgo biloba sarcotestas (GBS) and investigates the underlying mechanism in human MDA-MB-231 and mouse 4T-1 triple-negative breast cancer cells. Our results showed that 2-Hydroxy-6-tridecylbenzoic acid was isolated by cytotoxicity-guided fractionation where different fractions were assessed using MTT assay against MDA-MB-231 and 4T-1 cells. Colony formation assay showed that 2-Hydroxy-6-tridecylbenzoic acid significantly inhibited cell proliferation. The inhibition was associated with the enhancement of cytochrome P450 (CYP) 1B1 expression in a dose- and time-dependent manner and no significant change of CYP1A1 expression by qPCR and Western blot assays in MDA-MB-231 and 4T-1 cells. The mechanism was further demonstrated by the activation of aryl hydrocarbon receptor (AhR) pathway with the upregulation of AhR, AhR nuclear translocator (ARNT) and AhR-dependent xenobiotic response elements (XRE) activity. These findings may have implications for development of anticancer agents containing 2-Hydroxy-6-tridecylbenzoic acid as functional additives.

• Authors: Dayu Zhou, Chunying Jiang, Chenghao Fu, Ping Chang, Bin Yang, Jiadi Wu, Xiaohui Zhao, Shiliang Ma
• Journal: Natural product research (Nat Prod Res) Vol. 34 Issue 6 Pg. 893-897 (Mar 2020) ISSN: 1478-6427 [Electronic] England
• PMID: 30445863 (Publication Type: Journal Article)

Chemical References

• AHR protein, human
• Basic Helix-Loop-Helix Transcription Factors
• Benzoates
• Plant Extracts
• Receptors, Aryl Hydrocarbon
• Aryl Hydrocarbon Receptor Nuclear Translocator
• Ginkgo biloba extract
• CYP1A1 protein, human
• CYP1B1 protein, human
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP1B1

Topics

• Animals
• Aryl Hydrocarbon Receptor Nuclear Translocator (metabolism)
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Benzoates (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytochrome P-450 CYP1A1 (metabolism)
• Cytochrome P-450 CYP1B1 (metabolism)
• Female
• Ginkgo biloba (chemistry)
• Humans
• Mice
• Plant Extracts (pharmacology, therapeutic use)
• Receptors, Aryl Hydrocarbon (metabolism)
• Triple Negative Breast Neoplasms (drug therapy, pathology)