TY - JOUR AB - 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. AD - 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 AU - Lee,Dae,Hyung AU - Lim,In-Hye AU - Sung,Eon-Gi AU - Kim,Joo-Young AU - Song,In-Hwan AU - Park,Yoon,Ki AU - Lee,Tae-Jin DA - 2013/08/01 DO - 10.3892/or.2013.2487 EP - 938 IS - 2 JO - Oncol Rep KW - withaferin A MMP-9 TGF-β Caski pAkt PY - 2013 SN - 1021-335X 1791-2431 SP - 933 ST - Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway T2 - Oncology Reports TI - Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway UR - https://doi.org/10.3892/or.2013.2487 VL - 30 ER -