Kim Keun Ki, Kawano Yasuhiro, Yamazaki Yoshimitsu
Biotechnology Department, Miryang National University, 1025-1 Naei-dong, Miryang, Kyungnam, 627-702, Korea.
Anticancer Res. 2003 May-Jun;23(3B):2355-61.
In the screening of new anticancer agents, we found that a methanol extract of bamboo leaves induced rapid apoptosis in the human leukemia CMK-7 cell line.
The active compounds in the extract were isolated by chromatographic methods and their structures were determined by NMR and mass spectroscopy. Apoptosis by the compounds were evaluated in CMK-7 and human colon adenocarcinoma Colo320 DM cells by monitoring the caspase-3 activation and DNA cleavage.
The active compounds are 201-hydroxypurpurin-7 delta-lactone ethyl methyl diester (1) and the corresponding methyl phytyl diester (2). The apoptosis by compound 1 (0.3 to 0.1 microM for CMK-7 cells) was enhanced when the culture was briefly irradiated with a fluorescent lamp. This photodynamic induction of apoptosis by compound 1 was much stronger than that by a known photosensitizer, pyropheophorbidemethyl. Compound 2 was a weaker inducer of apoptosis than compound 1, but the apoptosis occurred after light irradiation.
The 201-hydroxypurpurin-7 delta-lactone esters are promising lead compounds as photosensitizers for photodynamic therapy of cancer.
在新型抗癌药物的筛选过程中,我们发现竹叶甲醇提取物可诱导人白血病CMK - 7细胞系快速凋亡。
通过色谱法分离提取物中的活性化合物,并利用核磁共振和质谱确定其结构。通过监测半胱天冬酶 - 3的激活和DNA裂解,评估这些化合物在CMK - 7和人结肠腺癌Colo320 DM细胞中诱导凋亡的情况。
活性化合物为201 - 羟基紫红素 - 7δ - 内酯甲乙二酸酯(1)和相应的甲基植基二酸酯(2)。当用荧光灯短暂照射培养物时,化合物1(对CMK - 7细胞为0.3至0.1微摩尔)诱导的凋亡增强。化合物1的这种光动力诱导凋亡作用比已知的光敏剂焦脱镁叶绿酸甲酯要强得多。化合物2诱导凋亡的能力比化合物1弱,但光照后会发生凋亡。
201 - 羟基紫红素 - 7δ - 内酯酯类作为癌症光动力治疗的光敏剂是很有前景的先导化合物。