Department of Medical Education, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Molecules. 2022 Nov 1;27(21):7410. doi: 10.3390/molecules27217410.
Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant's rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids.
姜黄香料含有姜黄素类化合物，这是在姜黄植物根茎中发现的多酚类化合物。这一类分子包括姜黄素、脱甲氧基姜黄素和双脱甲氧基姜黄素。我们使用前列腺癌细胞系 PC3、LNCaP、DU145 和 C42B 表明，姜黄素类化合物抑制细胞增殖（通过 MTT 测定法测量）并诱导类似凋亡的细胞死亡（通过 DNA/组蛋白 ELISA 测量）。铜螯合剂（亚铜试剂）和活性氧物质清除剂（硫脲用于羟基自由基、超氧化物歧化酶用于超氧阴离子、过氧化氢酶用于过氧化氢）显著抑制该反应，从而表明细胞内的铜与癌细胞中的姜黄素类化合物反应，通过 ROS 生成导致 DNA 损伤。我们进一步表明，补充铜的培养基使正常乳腺上皮细胞（MCF-10A）对姜黄素介导的生长抑制敏感，这通过降低细胞增殖来确定。铜补充导致 MCF-10A 细胞中铜转运蛋白 CTR1 和 ATP7A 的表达增加，而培养基中添加姜黄素则减弱了这种增加。我们提出，铜介导的、ROS 诱导的癌细胞选择性细胞死亡机制可能部分解释了姜黄素类化合物的抗癌作用。
