Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo

被引:6
作者
Xu, G. [1 ]
Niu, Z. [2 ]
Dong, J. [3 ]
Zhao, Y. [1 ]
Zhang, Y. [1 ]
Li, X. [4 ]
机构
[1] Zhengzhou Peoples Hosp, Zhengzhou 450003, Henan Province, Peoples R China
[2] Anyang Tumor Hosp, Anyang 455000, Henan Province, Peoples R China
[3] Zhengzhou First Peoples Hosp, Zhengzhou 450000, Henan Province, Peoples R China
[4] Henan Prov Peoples Hosp, Zhengzhou 450000, Henan Province, Peoples R China
关键词
noscapine; hepatocellular carcinoma; apoptosis; toxicity; BAX/BCL-2; RATIO; CANCER; CELLS; DEGRADATION; ACTIVATION; SURVIVAL; DELIVERY; RECEPTOR; TISSUES; PROTEIN;
D O I
10.4149/neo_2016_509
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been demonstrated as a promising anti-tumor compound against various cancers. However, the anti-cancer activity of noscapine in hepatocellular carcinoma has not been defined. In this study, we investigate the inhibitive effects of noscapine on human hepatocellular carcinoma (HCC) using both in vitro and in vivo models. In vitro proliferation assay showed that noscapine suppressed HepG2 and Huh7 cells in dose-and time-dependent manners. With a mouse xenograft model, noscapine showed notable inhibition on HCC tumor growth in vivo without suppression of body weight. Moreover, apoptotic induction and regulation of related signalings by noscapine were examined by nuclear DNA staining, TUNEL, and western blotting assays. Results showed that noscapine induced apoptosis in HCC cells both in vitro and in vivo. Further studies indicated that noscapine induced antive-capsase-3, cleavage PARP, and decreased the ratio of Bcl-2/Bax. Hence, these data indicates that noscapine selectively suppresses HCC cell growth through apoptosis induction, providing evidence for application of noscapine as a novel agent against human hepatocellular carcinoma.
引用
收藏
页码:726 / 733
页数:8
相关论文
共 31 条
[1]   Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent [J].
Aneja, Ritu ;
Dhiman, Neerupma ;
Idnani, Jyoti ;
Awasthi, Anshumali ;
Arora, Sudershan K. ;
Chandra, Ramesh ;
Joshi, Harish C. .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2007, 60 (06) :831-839
[2]   p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells [J].
Aneja, Ritu ;
Ghaleb, Amr M. ;
Zhou, Jun ;
Yang, Vincent W. ;
Joshi, Harish C. .
CANCER RESEARCH, 2007, 67 (08) :3862-3870
[3]   Anticancer activity of Noscapine, an opioid alkaloid in combination with Cisplatin in human non-small cell lung cancer [J].
Chougule, Mahavir ;
Patel, Apurva R. ;
Sachdeva, Pratik ;
Jackson, Tanise ;
Singh, Mandip .
LUNG CANCER, 2011, 71 (03) :271-282
[4]   Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio [J].
Chueh, Wei-Han ;
Lin, Jin-Yuarn .
FOOD CHEMISTRY, 2012, 132 (01) :252-260
[5]   Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study [J].
De Angelis, Roberta ;
Sant, Milena ;
Coleman, Michel P. ;
Francisci, Silvia ;
Baili, Paolo ;
Pierannunzio, Daniela ;
Trama, Annalisa ;
Visser, Otto ;
Brenner, Hermann ;
Ardanaz, Eva ;
Bielska-Lasota, Magdalena ;
Engholm, Gerda ;
Nennecke, Alice ;
Siesling, Sabine ;
Berrino, Franco ;
Capocaccia, Riccardo .
LANCET ONCOLOGY, 2014, 15 (01) :23-34
[6]   Gambogic acid induced tumor cell apoptosis by T lymphocyte activation in H22 transplanted mice [J].
Gu, Hongyan ;
You, Qidong ;
Liu, Wei ;
Yang, Yong ;
Zhao, Li ;
Qi, Qi ;
Zhao, Jie ;
Wang, Jia ;
Lu, Na ;
Ling, Hua ;
Guo, Qinglong ;
Wang, Xiaotang .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2008, 8 (11) :1493-1502
[7]   Induction of Bax protein and degradation of lamin A during p53-dependent apoptosis induced by chemotherapeutic agents in human cancer cell lines [J].
Ho, YS ;
Lee, HM ;
Chang, CR ;
Lin, JK .
BIOCHEMICAL PHARMACOLOGY, 1999, 57 (02) :143-154
[8]   Antitumor activity of noscapine in human non-small cell lung cancer xenograft model [J].
Jackson, Tanise ;
Chougule, Mahavir B. ;
Ichite, Nkechi ;
Patlolla, Ram R. ;
Singh, Mandip .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2008, 63 (01) :117-126
[9]   Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses [J].
Ke, Y ;
Ye, K ;
Grossniklaus, HE ;
Archer, DR ;
Joshi, HC ;
Kapp, JA .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2000, 49 (4-5) :217-225
[10]  
Khanmoradi M, 2014, IRAN J BASIC MED SCI, V17, P244