Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo.

Abstract

The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells.

• Authors: Yuichi Kinoshita, Katsuhiko Yoshizawa, Kei Hamazaki, Yuko Emoto, Takashi Yuri, Michiko Yuki, Nobuaki Shikata, Hiroshi Kawashima, Airo Tsubura
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 4 Pg. 1385-94 (Oct 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25109488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2
• 8,11,14-Eicosatrienoic Acid
• mead acid

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, pharmacology)
• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism)
• Cadherins (drug effects, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Neovascularization, Pathologic
• Vascular Endothelial Growth Factor A (drug effects, metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (drug effects, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (drug effects, metabolism)
• Xenograft Model Antitumor Assays