TY - JOUR
T1 - Docosahexaenoic acid (DHA) inhibits pro-angiogenic effects of breast cancer cells via down-regulating cellular and exosomal expression of angiogenic genes and microRNAs
AU - Aslan, Cynthia
AU - Maralbashi, Sepideh
AU - Kahroba, Houman
AU - Asadi, Milad
AU - Soltani-Zangbar, Mohammad Sadegh
AU - Javadian, Mahsa
AU - Shanehbandi, Dariush
AU - Baradaran, Behzad
AU - Darabi, Masood
AU - Kazemi, Tohid
N1 - Funding Information:
This study was done by grant from Immunology Research Center, Tabriz University of Medical Sciences (grant numbers 58550 and 95-011 ).
Funding Information:
This study was done by grant from Immunology Research Center, Tabriz University of Medical Sciences (grant numbers 58550 and 95-011).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Aims: Docosahexaenoic acid (DHA) as an omega 3 free fatty acid has been reported to exert anti-angiogenesis effects. However, our current understanding regarding the precise mechanisms of such effects is still limited. Exosomes secreted by cancer cells may act as angiogenesis promoters. The aim of the study was to determine altered expression levels of HIF-1α, TGF-β, VEGFR, Snail1, Snail2 and SOX2 and their regulating microRNAs in MDA-MB-231 and BT-474 cell lines after treatment with DHA in both normoxic and hypoxic conditions. Main methods: Human breast cancer cell lines including MDA-MB-231 and BT-474 were treated for 24 h with 100 uM DHA under normoxic and hypoxic conditions. Exosomes were isolated from untreated and treated cells and characterized by transmission electron microscopy (TEM) and western blotting. RNAs from cells and isolated exosomes were extracted and cDNAs were synthesized. Expression levels of miRNAs and their pro-angiogenic target genes were analyzed using quantitative real-time PCR (qRT-PCR). Key findings: We showed significant decrease in the expression of pro-angiogenic genes including HIF1-α, TGF-β, SOX2, Snail1, Snail2 and VEGFR in cells and also their secreted exosomes after treatment with DHA in normoxic and hypoxic conditions. Also the expression levels of tumor suppressor miRs including miR-101, miR-199, miR-342 were increased and the expression levels of oncomiRs including mir-382 and miR-21 were decreased after treatment with DHA in cells and exosomes. Significance: DHA can alter the expression of pro-angiogenic genes and microRNA contents in breast cancer cells and their derived-exosomes in favor of the inhibition of angiogenesis. Our data demonstrated new insight into DHA's anti-cancer action to target not only breast cancer cells but also their derived exosomes to suppress tumor angiogenesis.
AB - Aims: Docosahexaenoic acid (DHA) as an omega 3 free fatty acid has been reported to exert anti-angiogenesis effects. However, our current understanding regarding the precise mechanisms of such effects is still limited. Exosomes secreted by cancer cells may act as angiogenesis promoters. The aim of the study was to determine altered expression levels of HIF-1α, TGF-β, VEGFR, Snail1, Snail2 and SOX2 and their regulating microRNAs in MDA-MB-231 and BT-474 cell lines after treatment with DHA in both normoxic and hypoxic conditions. Main methods: Human breast cancer cell lines including MDA-MB-231 and BT-474 were treated for 24 h with 100 uM DHA under normoxic and hypoxic conditions. Exosomes were isolated from untreated and treated cells and characterized by transmission electron microscopy (TEM) and western blotting. RNAs from cells and isolated exosomes were extracted and cDNAs were synthesized. Expression levels of miRNAs and their pro-angiogenic target genes were analyzed using quantitative real-time PCR (qRT-PCR). Key findings: We showed significant decrease in the expression of pro-angiogenic genes including HIF1-α, TGF-β, SOX2, Snail1, Snail2 and VEGFR in cells and also their secreted exosomes after treatment with DHA in normoxic and hypoxic conditions. Also the expression levels of tumor suppressor miRs including miR-101, miR-199, miR-342 were increased and the expression levels of oncomiRs including mir-382 and miR-21 were decreased after treatment with DHA in cells and exosomes. Significance: DHA can alter the expression of pro-angiogenic genes and microRNA contents in breast cancer cells and their derived-exosomes in favor of the inhibition of angiogenesis. Our data demonstrated new insight into DHA's anti-cancer action to target not only breast cancer cells but also their derived exosomes to suppress tumor angiogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85088982878&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2020.118094
DO - 10.1016/j.lfs.2020.118094
M3 - Journal articles
C2 - 32673663
AN - SCOPUS:85088982878
SN - 0024-3205
VL - 258
JO - Life Sciences
JF - Life Sciences
M1 - 118094
ER -
