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S-烯丙基半胱氨酸是一种水溶性大蒜衍生物,在体内条件下可抑制人雄激素非依赖性前列腺癌异种移植瘤CWR22R的生长。

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

作者信息

Chu Qingjun, Lee Davy T W, Tsao Sai Wah, Wang Xianghong, Wong Yong Chuan

机构信息

Cancer Biology Group, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.

出版信息

BJU Int. 2007 Apr;99(4):925-32. doi: 10.1111/j.1464-410X.2006.06639.x. Epub 2006 Nov 28.

Abstract

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 alpha, beta and gamma-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 gamma-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.

摘要

目的

评估S-烯丙基半胱氨酸(SAC)对裸鼠体内人雄激素非依赖性(AI)前列腺癌异种移植瘤CWR22R的作用。尽管全球进行了广泛研究,但尚无有效方法控制前列腺癌的生长,我们之前报道过,大蒜的两种水溶性衍生物S-烯丙基半胱氨酸(SAC)和S-烯丙基巯基半胱氨酸(SAMC),在体外可通过恢复E-钙黏蛋白表达来抑制癌细胞侵袭。

材料与方法

通过免疫组化染色评估SAC对肿瘤细胞增殖标志物如Ki-67和增殖细胞核抗原,以及凋亡调节因子包括Bcl-2和裂解的半胱天冬酶-3的影响。通过E-钙黏蛋白及其结合蛋白α、β和γ-连环蛋白的免疫反应性检测SAC对前列腺癌侵袭的抑制作用。评估三个不同时间点(治疗开始、中期和结束)的血清前列腺特异性抗原(PSA)水平以及治疗后SAC对多个器官的毒性。

结果

SAC治疗导致CWR22R生长受到抑制,对裸鼠未检测到毒性作用。SAC诱导的生长减少与血清PSA水平和异种移植瘤增殖率的同时降低相关,同时通过恢复E-钙黏蛋白和γ-连环蛋白表达抑制侵袭。此外,SAC处理的肿瘤凋亡率增加,同时Bcl-2减少,裂解的半胱天冬酶-3增加。

结论

这些结果表明,这种源自大蒜的化合物可能是抑制AI前列腺癌的潜在治疗剂。

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