Ampelopsins A and C Induce Apoptosis and Metastasis through Downregulating AxL, TYRO3, and FYN Expressions in MDA-MB-231 Breast Cancer Cells

Cheng Huang; Yu-Ling Huang; Chia-Chi Wang; Yi-Ling Pan; Yu-Heng Lai; Hsiu-Chen Huang

doi:10.1021/acs.jafc.8b06444

Ampelopsins A and C Induce Apoptosis and Metastasis through Downregulating AxL, TYRO3, and FYN Expressions in MDA-MB-231 Breast Cancer Cells

J Agric Food Chem. 2019 Mar 13;67(10):2818-2830. doi: 10.1021/acs.jafc.8b06444. Epub 2019 Mar 4.

Authors

Cheng Huang^{1

2}, Yu-Ling Huang^{3

4}, Chia-Chi Wang⁵, Yi-Ling Pan⁵, Yu-Heng Lai⁶, Hsiu-Chen Huang⁵

Affiliations

¹ Department of Biotechnology and Laboratory Science in Medicine , National Yang-Ming University , Taipei 112 , Taiwan.
² Department of Earth and Life Sciences , University of Taipei , Taipei 100 , Taiwan.
³ National Research Institute of Chinese Medicine , No. 155-1, Section 2, Li-Nong Street , Beitou District, Taipei 11221 , Taiwan.
⁴ Department of Cosmetic Science , Chang Gung University of Science and Technology , No. 261, Wen-Hwa First Road , Kwei-shan, Taoyuan 333 , Taiwan.
⁵ Department of Applied Science , National Tsing Hua University , South Campus, No. 521, Nanda Road , Hsinchu 30014 , Taiwan.
⁶ Department of Chemistry , Chinese Culture University , Taipei 11114 , Taiwan.

PMID: 30789269
DOI: 10.1021/acs.jafc.8b06444

Abstract

Ampelopsins A and C are resveratrol oligostilbenes whose role in cancer development remains unknown. This study evaluated the antimetastatic and apoptosis-inducing properties of ampelopsins A and C in MDA-MB-231 cells. The IC₅₀ values of ampelopsins A and C against MDA-MB-231 cells at 72 h were 38.75 ± 4.61 and 2.71 ± 0.21 μM, respectively. However, at 24 h, ampelopsins A and C decreased cell metastasis significantly. Among the 71 proteins present on the human phosphoreceptor tyrosin kinase array, ampelopsin C decreased the phosphorylated protein level of AXL, Dtk (TYRO3), EphA2, EphA6, Fyn, Hck, and SRMS. Additionally, antiproliferation effects of ampelopsin C were enhanced when combined with luteolin and chrysin compared to either two or a single agent in MDA-MB-231 cells. Overall, ampelopsins A and C extracted from Vitis thunbergii are both novel antimetastatic agents and potential therapeutic targets in patients with breast cancer.

Keywords: AxL; FYN; MDA-MB-231; ampelopsin A; ampelopsin C.

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Axl Receptor Tyrosine Kinase
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / physiopathology
Cell Line, Tumor
Cell Proliferation / drug effects
Down-Regulation / drug effects
Female
Flavonoids / pharmacology*
Humans
Neoplasm Metastasis
Phosphorylation
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-fyn / genetics*
Proto-Oncogene Proteins c-fyn / metabolism
Receptor Protein-Tyrosine Kinases / genetics*
Receptor Protein-Tyrosine Kinases / metabolism

Substances

Antineoplastic Agents
Flavonoids
Proto-Oncogene Proteins
ampelopsin
Receptor Protein-Tyrosine Kinases
TYRO3 protein, human
FYN protein, human
Proto-Oncogene Proteins c-fyn
Axl Receptor Tyrosine Kinase
AXL protein, human