Dorai T, Cao Y C, Dorai B, Buttyan R, Katz A E
Molecular Urology Laboratory, Department of Urology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Prostate. 2001 Jun 1;47(4):293-303. doi: 10.1002/pros.1074.
Earlier work from our laboratory highlighted the therapeutic potential of curcumin (turmeric), used as a dietary ingredient and as a natural anti-inflammatory agent in India and other Southeast Asian countries. This agent was shown to decrease the proliferative potential and induce the apoptosis potential of both androgen-dependent and androgen-independent prostate cancer cells in vitro, largely by modulating the apoptosis suppressor proteins and by interfering with the growth factor receptor signaling pathways as exemplified by the EGF-receptor. To extend these observations made in vitro and to study the efficacy of this potential anti-cancer agent in vivo, the growth of LNCaP cells as heterotopically implanted tumors in nude mice was followed.
The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received a synthetic diet containing 2% curcumin for up to 6 weeks. At the end point, sections taken from the excised tumors were evaluated for pathology, cell proliferation, apoptosis, and vascularity.
Curcumin causes a marked decrease in the extent of cell proliferation as measured by the BrdU incorporation assay and a significant increase in the extent of apoptosis as measured by an in situ cell death assay. Moreover, a significant decrease in the microvessel density as measured by the CD31 antigen staining was also seen.
Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth, as exemplified by LNCaP in vivo, and has the potential to prevent the progression of this cancer to its hormone refractory state.
我们实验室早期的研究突出了姜黄素(姜黄)的治疗潜力,在印度和其他东南亚国家,姜黄素被用作饮食成分和天然抗炎剂。在体外实验中,这种物质被证明能降低雄激素依赖性和雄激素非依赖性前列腺癌细胞的增殖潜力并诱导其凋亡潜力,主要是通过调节凋亡抑制蛋白以及干扰生长因子受体信号通路,如表皮生长因子受体(EGF-受体)所体现的那样。为了拓展这些体外实验的观察结果,并研究这种潜在抗癌剂在体内的疗效,我们跟踪了LNCaP细胞在裸鼠体内异位植入肿瘤后的生长情况。
将雄激素依赖性LNCaP前列腺癌细胞培养后与基质胶混合,皮下注射到裸鼠体内。实验组接受含2%姜黄素的合成饮食,持续6周。在实验终点,对切除肿瘤的切片进行病理学、细胞增殖、凋亡和血管生成评估。
通过BrdU掺入实验测量,姜黄素使细胞增殖程度显著降低;通过原位细胞死亡实验测量,凋亡程度显著增加。此外,通过CD31抗原染色测量,微血管密度也显著降低。
姜黄素可能是一种具有潜在治疗作用的抗癌剂,因为它能显著抑制前列腺癌生长,如在体内对LNCaP细胞的实验所示,并且有潜力预防这种癌症发展到激素难治状态。