Department of Physiology, Mahidol University, Bangkok, Thailand.
Cell Biol Toxicol. 2011 Dec;27(6):413-23. doi: 10.1007/s10565-011-9196-4. Epub 2011 Jul 16.
Diarylheptanoids, isolated from the rhizome of Curcuma comosa Roxb., have several biological activities including anti-oxidant and anti-inflammation. The present study investigated the effect of five diarylheptanoids isolated from C. comosa rhizome on the proliferation of murine P388 leukemic cells. Compound-092, (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol, bearing a catechol moiety, was the most potent diarylheptanoid (IC(50) of 4 μM) in inhibiting P388 leukemic cell viability by causing DNA breakage and inducing apoptosis. Apoptotic cell death was characterized by the presence of chromatin condensation, formation of apoptotic bodies, DNA fragmentation, and externalization of plasma membrane phosphatidylserine. This compound increased caspase-3 activity about fivefold above the untreated control, decreased the intracellular reduced glutathione level, and impaired mitochondrial transmembrane potential. In the presence of Cu(II) ion, the compound exhibited a pro-oxidant activity causing DNA strand breakage and enhancing the anti-proliferative activity. The results provide evidence for the pro-oxidant activity of the diarylheptanoid bearing a catechol moiety in the induction of apoptosis in murine P388 leukemia.
从莪术根茎中分离得到的二芳庚烷类化合物具有多种生物活性，包括抗氧化和抗炎作用。本研究探讨了从莪术根茎中分离得到的五种二芳庚烷类化合物对鼠 P388 白血病细胞增殖的影响。化合物 092，（3S）-1-（3,4-二羟基苯基）-7-苯基-（6E）-6-庚烯-3-醇，带有儿茶酚部分，是最有效的二芳庚烷类化合物（IC50 为 4 μM），通过引起 DNA 断裂和诱导细胞凋亡来抑制 P388 白血病细胞活力。细胞凋亡的特征是染色质浓缩、凋亡小体形成、DNA 片段化和质膜磷脂酰丝氨酸外翻。该化合物使 caspase-3 活性比未处理的对照组增加了约五倍，降低了细胞内还原型谷胱甘肽水平，并损害了线粒体跨膜电位。在 Cu(II)离子存在下，该化合物表现出促氧化剂活性，导致 DNA 链断裂，并增强了抗增殖活性。这些结果为具有儿茶酚部分的二芳庚烷类化合物在诱导鼠 P388 白血病细胞凋亡中的促氧化剂活性提供了证据。
