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S-allylcysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions

机译:s-烯丙基半胱氨酸,一种水溶性大蒜衍生物,在体内条件下抑制人雄激素非依赖性前列腺癌异种移植物CWR22R的生长

摘要

OBJECTIVE: To evaluate the effect of S-allylcysteine (SAC) on CWR22R, a human androgen-independent (AI) prostate cancer xenograft, in nude mice. Despite extensive research worldwide there is no effective way to control the growth of prostate cancer, and we previously reported that SAC and S- allylmercaptocysteine (SAMC), two water-soluble derivatives of garlic, inhibit cancer cell invasion through restoration of E-cadherin expression in vitro. MATERIALS AND METHODS: The effects of SAC on tumour cell proliferation markers such as Ki-67 and proliferating cell nuclear antigen, and apoptotic regulators including Bcl-2 and cleaved caspase-3, were assessed by immunohistochemical staining. The inhibitory effects of SAC on prostate cancer invasion was examined by immunoreactivity of E-cadherin and its binding proteins α, β and γ-catenins. The serum prostate-specific antigen (PSA) level at three different times (initiation, middle and end of treatment) and toxicity of SAC on several organs after treatment were assessed. RESULTS: Treatment with SAC resulted in inhibition of the growth of CWR22R, with no detectable toxic effect on nude mice. The SAC-induced growth reduction was correlated with a concurrent reduction in serum PSA level and proliferation rate of xenografts, together with an inhibition of invasion through the restoration of E-cadherin and γ-catenin expression. Furthermore, the apoptotic rate of SAC-treated tumours increased together with a decrease in Bcl-2 and increase in cleaved caspase-3. CONCLUSION: These results suggest that this garlic-derived compound might be a potential therapeutic agent for suppressing AI prostate cancer. © 2006 The Authors.
机译:目的:评估S-烯丙基半胱氨酸(SAC)对人雄激素非依赖性(AI)前列腺癌异种移植物CWR22R的影响。尽管在全球范围内进行了广泛的研究,但尚无有效的方法来控制前列腺癌的生长,而且我们之前曾报道SAC和大蒜的两种水溶性衍生物S-烯丙基巯基半胱氨酸(SAMC)通过恢复E-钙黏着蛋白的表达来抑制癌细胞的侵袭。体外。材料与方法:通过免疫组织化学染色评估了SAC对肿瘤细胞增殖标志物(例如Ki-67和增殖细胞核抗原)以及凋亡调节剂(包括Bcl-2和裂解的caspase-3)的影响。通过E-钙粘着蛋白及其结合蛋白α,β和γ-连环蛋白的免疫反应性检查了SAC对前列腺癌侵袭的抑制作用。评估了三个不同时间(治疗开始,治疗的中间和结束)的血清前列腺特异性抗原(PSA)水平以及SAC对治疗后几个器官的毒性。结果:SAC处理可抑制CWR22R的生长,并且对裸鼠没有可检测到的毒性作用。 SAC诱导的生长减少与同时降低血清PSA水平和异种移植物的增殖率有关,并通过恢复E-钙黏着蛋白和γ-连环蛋白的表达来抑制侵袭。此外,SAC处理的肿瘤的凋亡率增加,同时Bcl-2减少和caspase-3裂解增加。结论:这些结果表明,这种大蒜来源的化合物可能是抑制AI前列腺癌的潜在治疗剂。 ©2006作者。

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