Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway

Lee,Dae Hyung; Lim,In-Hye; Sung,Eon-Gi; Kim,Joo-Young; Song,In-Hwan; Park,Yoon Ki; Lee,Tae-Jin

doi:10.3892/or.2013.2487

August 2013 Volume 30 Issue 2

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August 2013 Volume 30 Issue 2

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Article

Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway

Authors:
- Dae Hyung Lee
- In-Hye Lim
- Eon-Gi Sung
- Joo-Young Kim
- In-Hwan Song
- Yoon Ki Park
- Tae-Jin Lee
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynecology, Yeungnam University, Daegu 705-717, Republic of Korea, Department of Anatomy, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea
Pages: 933-938
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Published online on: May 23, 2013

https://doi.org/10.3892/or.2013.2487
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Abstract

Withaferin A (Wit A), a steroidal lactone isolated from Withania somnifera, exhibits anti-inflammatory, immunomodulatory and anti-angiogenic properties and antitumor activities. In the present study, we investigated the effects of Wit A on protease-mediated invasiveness of the human metastatic cancer cell lines Caski and SK-Hep1. We found that treatment with Wit A resulted in marked inhibition of the TGF‑β‑induced increase in expression and activity of matrix metalloproteinase (MMP)‑9 in Caski cell line. These effects of Wit A were dose-dependent and showed a correlation with suppression of MMP‑9 mRNA expression levels. Treatment with Wit A resulted in an ~1.6-fold induction of MMP-9 promoter activity, which was also suppressed by treatment with Wit A in Caski cells. We found that treatment with Wit A resulted in inhibition of TGF‑β‑induced phosphorylation of Akt, which was involved in the downregulation of expression of MMP-9 at the protein level. Introduction with constitutively active (CA)‑Akt resulted in a partial increase in the secretion of TGF-β-induced MMP-9 blocked by treatment with Wit A in Caski cells. According to these results, Wit A may inhibit the invasive and migratory abilities of Caski cells through a reduction in MMP-9 expression through suppression of the pAkt signaling pathway. These findings indicate that use of Wit A may be an effective strategy for control of metastasis and invasiveness of tumors.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway

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