SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice

Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified. Here, we examined the effect of SRT1720, a SIRT1 activator, on lung metastasis of breast cancer cells. 4T1 breast cancer cells were subcutaneously implanted into syngeneic BALB/c mice and SRT1720 was administered alone or with an antitumor agent, cisplatin. As expected, cisplatin decreased the lung metastasis score, whereas SRT1720 increased metastasis irrespective of cisplatin. In the primary tumors, cisplatin suppressed the mRNA level of angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting gene product of breast cancer, but SRT1720 reduced the effectiveness of cisplatin. The results obtained with animal experiments were in accordance with those in human cancer cells; SRT1720 significantly increased the amount of VEGF secreted from MDA-MB-231 cells. Moreover, a transendothelial cell migration assay showed that SRT1720 promotes the migration of MDA-MB-231 cells across an endothelial cell layer despite the presence of cisplatin. These findings imply that SRT1720 promotes the pulmonary metastasis of breast cancer cells and SIRT1 may be an important target for suppressing metastasis to the lung.

Suzuki, Kensuke
Hayashi, Ryuji
Ichikawa, Tomomi
Imanishi, Shingo
Yamada, Toru
Inomata, Minehiko
Miwa, Toshiro
Matsui, Shoko
Usui, Isao
Urakaze, Masaharu
Matsuya, Yuji
Ogawa, Hirofumi
Sakurai, Hiroaki
Saiki, Ikuo
Tobe, Kazuyuki
Item Type: 
Journal Article
Publication Title: 
Oncology Reports
Journal Abbreviation: 
Oncol. Rep.
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 22470132

Turabian/Chicago Citation

Kensuke Suzuki, Ryuji Hayashi, Tomomi Ichikawa, Shingo Imanishi, Toru Yamada, Minehiko Inomata, Toshiro Miwa, Shoko Matsui, Isao Usui, Masaharu Urakaze, Yuji Matsuya, Hirofumi Ogawa, Hiroaki Sakurai, Ikuo Saiki and Kazuyuki Tobe. 2012-06. "SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice." Oncology Reports 27: 6: 1726-1732. 10.3892/or.2012.1750.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.3892/or.2012.1750 | issn = 1791-2431 | volume = 27 | pages = 1726-1732 | last = Suzuki | first = Kensuke | coauthors = Hayashi, Ryuji, Ichikawa, Tomomi, Imanishi, Shingo, Yamada, Toru, Inomata, Minehiko, Miwa, Toshiro, Matsui, Shoko, Usui, Isao, Urakaze, Masaharu, Matsuya, Yuji, Ogawa, Hirofumi, Sakurai, Hiroaki, Saiki, Ikuo, Tobe, Kazuyuki | title = SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice | journal = Oncology Reports | date = 2012-06 | pmid = | pmc = }} </ref>