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This dissertation, "S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), Water Soluble Garlic Derivatives, Suppress Growth and Invasion of Androgen-independent Prostate Cancer, Under in Vitro and in Vivo Conditions" by Qingjun, Chu, 褚慶軍, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author.
Abstract:
Abstract of thesis entitled
S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), water soluble garlic derivatives, suppress growth and invasion of androgen-independent prostate cancer, under in vitro and in vivo conditions
Submitted by
Mr. Chu Qingjun
For the degree of Doctor of Philosophy at the University of Hong Kong
in October 2006
Prostate cancer is one of the most frequent invasive cancers in men in the Western society and becomes more common in China including Hong Kong. To date, there is no truly effective approach to control the growth of prostate cancer at androgen-independent (AI) and metastatic stages. Therefore, it is necessary to develop new strategies to suppress the progression of AI and metastatic prostate cancer. The aims of this study were to investigate whether SAC and SAMC, two water soluble garlic derivatives, had any effect on the invasiveness of AI prostate cancer cells, and the growth of AI prostate cancer xenografts in nude mice, as well as the underlying mechanisms responsible for their anticancer effects.
In the in vitro study, using colony forming assay, the results showed that SAC and SAMC were able to suppress the clonogenic ability of AI prostate cancer cells PC-3 and DU145. In addition, using proliferation, Wound Closure and Matrigel Invasion 2assays, SAC and SAMC were shown to inhibit the proliferation, migration and invasion ability of these cells. These inhibitory effects on invasion of prostate cancer cells were associated with the inhibition of epithelial-mesenchymal transition (EMT), as evidenced by the increased expression of epithelial markers and with a concurrent decrease in expression of mesenchymal markers together with a change in cell morphology, suggesting that they may be potential agents in the treatment of invasive cancers. More importantly, SAC and SAMC treatments led to restoration of E-cadherin expression at both transcription and protein levels. In contrast, the expression of E-cadherin repressor Snail, was reduced in the SAC and SAMC treated cells. Similar results were also observed in three other types of cancer cells Skov-3 (ovary), CNE-3 (nasopharynx) and EC109 (esophagus), indicating that the suppressive effect of SAC and SAMC on invasion of cancer cells may not be restricted only to prostate cancer cells.
In the in vivo study, treatment of SAC and SAMC resulted in inhibition of growth of CWR22R xenografts associated with a concurrent decrease in serum PSA level, without any detectable toxicity on nude mice. In addition, using immunohistochemistry, the results showed for the first time that SAC and SAMC suppressed the growth of AI prostate cancer xenografts through inhibition of cell proliferation by suppressing its markers Ki-67 and PCNA as well as invasion of cancer cells via restoring the expression of E-cadherin and its binding protein γ-catenin. Furthermore, the apoptotic rate of SAC and SAMC treated tumors was 3increased together with a decrease in Bcl-2 and an increase in cleaved caspase-3 expression.
In conclusion, SAC and SAMC were able to suppress the proliferation and invasion of cancer cells through restoration of E-cadherin function, and inhibit the growth of AI prostate cancer xenografts mediated by suppression of prolif
