Abstract |
An inability to control cancer cell invasion and metastasis is the leading cause of death in patients with cancer. The present study was performed to determine the anti-invasive effect of Kalopanaxsaponin A (KPS-A) on matrix metalloproteinase-9 (MMP-9)-meidated invasion in phorbol 12-myristate 13-acetate (PMA)-stimulated human oral squamous cell carcinoma (OSCC) cells and a murine xenograft model of human OSCC. KPS-A, isolated from Kalopanax pictus, inhibited PMA-induced proliferation and invasion as well as PMA-induced MMP-9 expression and secretion at non-cytotoxic doses. KPS-A treatment reduced the stability of PMA-induced MMP-9 mRNA and inhibited the PMA-induced cytoplasmic translocation of HuR. In PMA-treated cells, KPS-A treatment resulted in the intracellular accumulation of MMP-9 and suppressed Ras-associated binding 1A (Rab1A) expression. KPS-A treatment suppressed PMA-induced phosphorylation of extracellular signal regulated kinase (ERK)1/2 and Akt. Furthermore, the oral administration of KPS-A led to substantial inhibition of tumor growth and the expression of proliferating cell nuclear antigen ( PCNA), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), HuR, and Rab1A in the tumor tissues of mice inoculated with YD-10B OSCC cells. Collectively, KPS-A inhibits the invasiveness of oral cancer by reducing HuR-mediated MMP-9 mRNA stability and Rab1A-mediated MMP-9 secretion via ERK1/2 and phosphatidylinositide 3-kinase (PI3K)/Akt. Therefore, KPS-A is a promising anti-invasive agent.
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Authors | Young Sun Hwang, Kwang-Kyun Park, Won-Yoon Chung |
Journal | Biological & pharmaceutical bulletin
(Biol Pharm Bull)
Vol. 35
Issue 3
Pg. 289-300
( 2012)
ISSN: 1347-5215 [Electronic] Japan |
PMID | 22382313
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- RNA, Messenger
- Saponins
- kalopanax saponin A
- Oleanolic Acid
- Matrix Metalloproteinase 9
- Tetradecanoylphorbol Acetate
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology, therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, metabolism, pathology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Female
- Humans
- Matrix Metalloproteinase 9
(genetics)
- Mice
- Mice, Nude
- Mouth Neoplasms
(pathology)
- Neoplasm Invasiveness
- Oleanolic Acid
(analogs & derivatives, pharmacology, therapeutic use)
- Protein Transport
(drug effects)
- RNA, Messenger
(metabolism)
- Saponins
(pharmacology, therapeutic use)
- Tetradecanoylphorbol Acetate
(pharmacology)
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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