Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo

被引:8
作者
Hsia, Te-Chun [1 ,2 ]
Peng, Shu-Fen [3 ,4 ]
Chueh, Fu-Shin [5 ]
Lu, Kung-Wen [6 ]
Yang, Jiun-Long [7 ]
Huang, An-Cheng [7 ]
Hsu, Fei-Ting [4 ]
Wu, Rick Sai-Chuen [8 ,9 ]
机构
[1] China Med Univ, Dept Resp Therapy, Taichung 406, Taiwan
[2] China Med Univ Hosp, Dept Internal Med, Taichung 404, Taiwan
[3] China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan
[4] China Med Univ, Dept Biol Sci & Technol, Taichung 406, Taiwan
[5] Asia Univ, Dept Food Nutr & Hlth Biotechnol, Taichung 413, Taiwan
[6] China Med Univ, Sch Postbaccalaureate Chinese Med, Coll Chinese Med, Taichung 406, Taiwan
[7] St Marys Jr Coll Med Nursing & Management, Dept Nursing, Yilan 266, Taiwan
[8] China Med Univ Hosp, Dept Anesthesiol, Taichung 404, Taiwan
[9] China Med Univ, Dept Anesthesiol, Taichung 404, Taiwan
关键词
BDMC; glioblastoma (GBM) 8401; luc2; cells; apoptosis; xenograft; BAX; Bcl-2; CYTOCHROME-C RELEASE; XIAP; MULTIFORME; CANCER; PHYTOCHEMICALS; RADIOTHERAPY; TEMOZOLOMIDE; CONCOMITANT; EXPRESSION; SORAFENIB;
D O I
10.3390/ijms23010538
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.
引用
收藏
页数:15
相关论文
共 52 条
[1]   Glioblastoma multiforme: a review of where we have been and where we are going [J].
Adamson, Cory ;
Kanu, Okezie O. ;
Mehta, Ankit I. ;
Di, Chunhui ;
Lin, Ningjing ;
Mattox, Austin K. ;
Bigner, Darell D. .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2009, 18 (08) :1061-1083
[2]  
[Anonymous], 2007, ACTA NEUROPATHOL, DOI DOI 10.1007/s00401-007-0243-4
[3]   Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status [J].
Brandes, Alba A. ;
Tosoni, Alicia ;
Franceschi, Enrico ;
Sotti, Guido ;
Frezza, Giampiero ;
Amista, Pietro ;
Morandi, Luca ;
Spagnolli, Federica ;
Ermani, Mario .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (08) :1275-1279
[4]   Vasculogenesis: a crucial player in the resistance of solid tumours to radiotherapy [J].
Brown, J. M. .
BRITISH JOURNAL OF RADIOLOGY, 2014, 87 (1035)
[5]   Chemical-induced apoptosis: Formation of the Apaf-1 apoptosome [J].
Cain, K .
DRUG METABOLISM REVIEWS, 2003, 35 (04) :337-363
[6]   Curcumin alleviates ischemia reperfusion-induced late kidney fibrosis through the APPL1/Akt signaling pathway [J].
Chen Hongtao ;
Fan Youling ;
Huang Fang ;
Peng Huihua ;
Zhong Jiying ;
Zhou Jun .
JOURNAL OF CELLULAR PHYSIOLOGY, 2018, 233 (11) :8588-8596
[7]   Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells [J].
Chen, HW ;
Huang, HC .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (06) :1029-1040
[8]   Hyperforin Suppresses Tumor Growth and NF-κB-mediated Anti-apoptotic and Invasive Potential of Non-small Cell Lung Cancer [J].
Chen, Wei-Ting ;
Chen, Ying-Kai ;
Lin, Song-Shei ;
Hsu, Fei-Ting .
ANTICANCER RESEARCH, 2018, 38 (04) :2161-2167
[9]   Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment [J].
Chikara, Shireen ;
Nagaprashantha, Lokesh Dalasanur ;
Singhal, Jyotsana ;
Horne, David ;
Awasthi, Sanjay ;
Singhal, Sharad S. .
CANCER LETTERS, 2018, 413 :122-134
[10]   Auricularia polytricha aqueous extract supplementation decreases hepatic lipid accumulation and improves antioxidative status in animal model of nonalcoholic fatty liver [J].
Chiu, Wan-Chun ;
Yang, Hsu-Hui ;
Chiang, Shu-Chi ;
Chou, Yu-Xuan ;
Yang, Hui-Ting .
BIOMEDICINE-TAIWAN, 2014, 4 (02) :29-38