Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway
- Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway
- 이태진; 이대형; 임인혜; 성언기; 송인환; 김주영; 박윤기
- MATRIX METALLOPROTEINASES; PROGNOSTIC MARKER; CANCER CELLS; EXPRESSION; CARCINOMA; INVASION; APOPTOSIS; GROWTH; TIMP-1
- Issue Date
- SPANDIDOS PUBL LTD
- ONCOLOGY REPORTS, v.30, no.2, pp.933 - 938
- 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-Hepl. We found that treatment with Wit A resulted in marked inhibition of the TGF-beta-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 similar to 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-beta-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-beta-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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