Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract
Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract
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DOI：
10.1016/j.fct.2010.06.006
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发表时间：
2010-08-01
影响因子：
4.3
通讯作者：
Cho, Somi Kim
中科院分区：
文献类型：
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作者：
Kim, Hana;Moon, Jeong Yong;Cho, Somi Kim
巨柑 (Dangyuja) 含有大量具有健康相关特性的黄酮类化合物。尽管之前的数据已经揭示了一些柑橘属物种的抗癌功效，但叶子提取物这种活性的潜在分子机制尚未得到详细研究。本研究的目的是评估柑橘叶对五种人类癌细胞系的细胞毒性作用，并确定当柚子叶的氯仿成分 (CF) 引起细胞死亡的可能机制。在测试的细胞系中，Dangyuja 的 CF 强烈降低了 HeLa 细胞的存活率。 CF处理诱导抗凋亡Bcl-2表达下调，导致半胱天冬酶的蛋白水解激活和聚（ADP-核糖）聚合酶（PARP）蛋白的降解。分别通过流式细胞术和DNA片段分析证实了细胞生长的抑制和细胞凋亡的诱导。通过液相色谱-电喷雾电离串联质谱（LC-ESI-MS/MS）鉴定CF的主要成分为异紫芩素、紫芩素、四甲基-O-异黄芩素、川陈皮素、橘皮素和5-羟基-6,7,8,3',4'-五甲氧基黄酮。我们的研究结果表明，Dangyuja 叶的 CF 是功能性多甲氧基黄酮的极好来源，它可能有助于预防宫颈癌，并可能成为治疗某些恶性肿瘤的有用药物。 (C) 2010 Elsevier Ltd. 保留所有权利。
Citrus grandis Osbeck (Dangyuja) has a high content of flavonoids with health-related properties. Although previous data have revealed the anticancer potency of some Citrus species, the underlying molecular mechanisms of this activity by leaf extracts have not been studied in detail. The purpose of this study was to evaluate the cytotoxic effects of citrus leaves on five human cancer cell lines and to determine the possible mechanisms of cell death elicited by the chloroform fraction (CF) of the Dangyuja leaf. The CF of Dangyuja strongly decreased the survival rate of HeLa cells, among the tested cell lines. CF treatment induced the down-regulation of anti-apoptotic Bcl-2 expression, resulting in the proteolytic activation of caspases and the degradation of poly (ADP-ribose) polymerase (PARP) protein. Arrested cell growth and induction of apoptosis were confirmed by flow cytometry and DNA fragmentation analysis, respectively. The major components of the CF were identified as isosinensetin, sinensetin, tetramethyl-O-isoscutellarein, nobiletin, tangeretin, and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our results suggest that the CF of Dangyuja leaves is an excellent source of functional polymethoxylated flavones, which may help prevent cervical cancer and may potentially be a useful agent for the treatment of certain malignancies. (C) 2010 Elsevier Ltd. All rights reserved.