Thao Nguyen Phuong, Cuong Nguyen Xuan, Luyen Bui Thi Thuy, Nam Nguyen Hoai, Cuong Pham Van, Thanh Nguyen Van, Nhiem Nguyen Xuan, Hanh Tran Thi Hong, Kim Eun-Ji, Kang Hee-Kyoung, Kiem Phan Van, Minh Chau Van, Kim Young Ho
Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST).
Chem Pharm Bull (Tokyo). 2013;61(10):1044-51. doi: 10.1248/cpb.c13-00490.
Using various chromatographic methods, four new steroids, astropectenols A-D (1-4), along with three known compounds (5-7) were isolated from a methanol extract of the starfish Astropecten polyacanthus. The structure elucidation was confirmed by spectroscopic methods, including one dimensional (1D)-, 2D-NMR and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The CH2Cl2 fraction and compound 7 exhibit potent cytotoxic effects against HL-60 human leukemia cells with the IC50 of 8.29 µg/mL and 2.70 µM, respectively, comparing to the positive control, mitoxantrone (IC50=6.80 µM). When HL-60 cells were treated with the CH₂Cl₂ fraction or compound 7, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. Investigations for the possible mechanism underlying the induction of apoptosis showed that CH₂Cl₂ fraction or compound 7 induced apoptosis through down-regulation of Bcl-2, up-regulation of Bax, cleavage of caspase-9, cleavage of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) in HL-60 cells. Furthermore, the apoptosis induction of HL-60 cell by CH₂Cl₂ fraction or compound 7 was attended by the decreasing of phospho-extracellular signal-regulated kinase (ERK) 1/2 and C-myc. These results indicated that the CH₂Cl₂ fraction and compound 7 could induce the apoptosis of HL-60 cells via the inactivation of ERK 1/2 and the decrease of C-myc. Our finding suggested the potential using of the CH₂Cl₂ fraction and compound 7 for leukemia treatment.
采用多种色谱方法，从多棘海燕海星的甲醇提取物中分离出4种新甾体化合物——海燕甾醇A - D（1 - 4）以及3种已知化合物（5 - 7）。通过光谱方法，包括一维（1D）-、二维核磁共振（2D - NMR）和傅里叶变换离子回旋共振质谱（FT - ICR - MS）确定了其结构。与阳性对照米托蒽醌（IC50 = 6.80 μM）相比，二氯甲烷萃取物和化合物7对HL - 60人白血病细胞表现出较强的细胞毒性作用，IC50分别为8.29 μg/mL和2.70 μM。当用二氯甲烷萃取物或化合物7处理HL - 60细胞时，观察到了一些凋亡事件，如染色质浓缩和亚G1期亚二倍体细胞群体增加。对凋亡诱导潜在机制的研究表明，二氯甲烷萃取物或化合物7通过下调HL - 60细胞中的Bcl - 2、上调Bax、切割caspase - 9、切割caspase - 3和切割聚（ADP - 核糖）聚合酶（PARP）诱导凋亡。此外，二氯甲烷萃取物或化合物7诱导HL - 60细胞凋亡伴随着磷酸化细胞外信号调节激酶（ERK）1/2和C - myc的减少。这些结果表明，二氯甲烷萃取物和化合物7可通过ERK 1/2失活和C - myc减少诱导HL - 60细胞凋亡。我们的发现提示二氯甲烷萃取物和化合物7在白血病治疗方面具有潜在应用价值。
