Metabolism of curcumin and induction of mitotic catastrophe in human cancer cells
Metabolism of curcumin and induction of mitotic catastrophe in human cancer cells
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DOI：
10.1002/mnfr.200800029
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发表时间：
2008-09-01
影响因子：
5.2
通讯作者：
Metzler, Manfred
中科院分区：
文献类型：
--
作者：
Dempe, Julia S.;Pfeiffer, Erika;Metzler, Manfred
在培养的细胞中，姜黄素（CUR）通过干扰有丝分裂并导致细胞核碎裂和微管破坏而导致细胞死亡，这一过程称为有丝分裂灾难。为了阐明已知的CUR代谢产物六氢-CUR（HHC）和CUR-glucuronide（CUR-gluc）在有丝分裂灾难中的作用，研究了CUR在具有不同CUR代谢的三种人癌细胞系中的作用。在石川和HepG 2细胞中，CUR代谢为HHC和少量八氢CUR（OHC），而在HT 29细胞中唯一的代谢是形成CUR-gluc。尽管它们的代谢不同，但所有三种细胞系统都对CUR反应为G2/M期停滞和有丝分裂灾难。细胞的分级显示，在ER和胞质溶胶中的CUR浓度比在孵育培养基中的CUR浓度高1倍Lip，分别为约150和8。与CUR相反，代谢产物HHC和自发降解产物在石川细胞中未引起任何影响。这些结果表明，有丝分裂灾难的病原体是母CUR分子，而还原代谢和化学降解使CUR失活。
In Cultured cells, curcumin (CUR) causes cell death by interfering with mitosis and leading to fragmented nuclei and disrupted microtubules, a process named mitotic catastrophe. In order to clarify the role of the known CUR metabolites hexahydro-CUR (HHC) and CUR-glucuronide (CUR-gluc) in mitotic catastrophe, the effects of CUR were studied in three human cancer cell lines with different metabolism of CUR. In Ishikawa and HepG2 cells, CUR was metabolized to HHC and small amounts of octahydro-CUR (OHC), whereas the only metabolism in HT29 cells was the formation of CUR-gluc. Despite their different metabolism, all three cell systems responded to CUR with arrest in G2/M phase and mitotic catastrophe. Fractionation of the cells showed that concentrations of CUR were higher in the ER and cytosol than in the incubation medium by a factor Of Lip to about 150 and 8, respectively. In contrast to CUR, the metabolite HHC and the products of spontaneous degradation did not elicit any effects in Ishikawa cells. These results imply that the causative agent of mitotic catastrophe is the parent CUR molecule, whereas reductive metabolism and chemical degradation render CUR inactive.