Abstract
Smilax glabra Roxb. (SGR) has been used as a traditional medicine for brucellosis and syphilis. In this study, we investigated whether nontoxicological levels of water extract of SGR (WESGR) are effective for suppressing steps in the progression of prostate cancer, such as collagen-mediated migration and adhesion and identified the target molecule responsible for such effects. We found that nontoxicological levels of WESGR did not attenuate PC3 and LNCaP cell adhesion to serum but did significantly do so with collagen. In addition, using the Boyden chamber assay, we found that nontoxicological levels of WESGR did not inhibit the migration of PC3 and LNCaP cells to a serum-coated area but did significantly attenuate migration to a collagen-coated area. Interestingly, the expression of α2β1 integrin, a known receptor of collagen, was not affected by ectopic administration of WESGR. However, WESGR significantly attenuated the expression of β1 integrin, but not α2 integrin when PC3 and LNCaP cells were placed on a collagen-coated plate, resulting in attenuation of focal adherent kinase phosphorylation. Finally, 5-O-caffeoylquinic acid was determined as a functional single component which is responsible for antiprostate cancer effects of WESGR. Taken together, our results suggest a novel molecular mechanism for WESGR-mediated antiprostate cancer effects at particular steps such as with migration and adhesion to collagen, and it could provide the possibility of therapeutic use of WESGR against prostate cancer progression.
Highlights
Prostate cancer is the second most common cancer in males, with reports stating that over 80% of cases are detected after age 65 [1]
We investigated the effects of nontoxicological levels of water extract of SGR (WESGR)
These results suggest that the use of nontoxicological levels of WESGR could be an effective way to attenuate the progression of prostate cancer during particular stages, such as prostate cancer
Summary
Prostate cancer is the second most common cancer in males, with reports stating that over 80% of cases are detected after age 65 [1]. The development of anticancer therapeutics with lower cytotoxicity and that target the inhibition of metastatic events such as cell migration and invasion could lead to an effective cure for prostate cancer, metastatic CRPC (mCRPC). Bonkhoff et al reported that the expression of α2β1 integrin is upregulated in lymph node metastases as compared to primary prostate tumors [14], suggesting that α2β1 integrin is a potential therapeutic target for prostate tumorigenesis, especially for mCRPC. An anticancer activity of SGR has been suggested against hepatocarcinomas [20,21], and a glycoprotein, SGF2, which is isolated from SGR has been reported to have antiproliferative effects on MCF-7 breast cancer cells [22]. We estimated the single components of WESGR through HPLC-MS/MS analysis
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