Escitalopram oxalate induces apoptosis in U-87MG cells and autophagy in GBM8401 cells

被引:39
作者
Chen, Vincent Chin-Hung [1 ,2 ]
Hsieh, Yi-Hsien [3 ,4 ,5 ]
Chen, Li-Jeng [4 ]
Hsu, Tsai-Ching [3 ,4 ,6 ]
Tzang, Bor-Show [3 ,4 ,5 ,6 ]
机构
[1] Chang Gung Univ, Dept Psychiat, Taoyuan, Taiwan
[2] Chiayi Chang Gung Mem Hosp, Dept Psychiat, Chiayi, Taiwan
[3] Chung Shan Med Univ Hosp, Clin Lab, Taichung, Taiwan
[4] Chung Shan Med Univ, Inst Biochem Microbiol & Immunol, Taichung, Taiwan
[5] Chung Shan Med Univ, Sch Med, Dept Biochem, Taichung, Taiwan
[6] Chung Shan Med Univ, Immunol Res Ctr, Taichung, Taiwan
关键词
glioblastoma multiforme; brain cancer; selective serotonin reuptake inhibitor; escitalopram oxalate; U-87MG; MAJOR DEPRESSIVE DISORDER; P-GLYCOPROTEIN; DRUG-DELIVERY; CANCER; GLIOBLASTOMA; BRAIN; ANTIDEPRESSANT; PHARMACOKINETICS; MECHANISMS; MANAGEMENT;
D O I
10.1111/jcmm.13372
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Glioblastoma multiforme (GBM) is recognized as a most aggressive brain cancer with the worst prognosis and survival time. Owing to the anatomic location of gliomas, surgically removing the tumour is very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Therefore, therapeutic strategies for malignant glioma must urgently be improved. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have cytotoxic effect on certain cancers. Considering as a more superior SSRI, escitalopram oxalate exhibits favourable tolerability and causes generally mild and temporary adverse events. However, limited information is revealed about the influence of escitalopram oxalate on GBM. Therefore, an attempt was made herein to explore the effects of escitalopram oxalate on GBM. The experimental results revealed that escitalopram oxalate significantly inhibits the proliferation and invasive ability of U-87MG cells and significantly reduced the expressions of cell cycle inhibitors such as Skp2, P57, P21 and P27. Notably, escitalopram oxalate also induced significant apoptotic cascades in U-87MG cells and autophagy in GBM8401 cells. An animal study indicated that escitalopram oxalate inhibits the proliferation of xenografted glioblastoma in BALB/c nude mice. These findings implied that escitalopram oxalate may have potential in treatment of glioblastomas.
引用
收藏
页码:1167 / 1178
页数:12
相关论文
共 48 条
[1]   Escitalopram for the treatment of major depressive disorder in youth [J].
Ahn, Joon-Ho ;
Patkar, Ashwin A. .
EXPERT OPINION ON PHARMACOTHERAPY, 2011, 12 (14) :2235-2244
[2]   Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters [J].
Andersen, Jacob ;
Kristensen, Anders S. ;
Bang-Andersen, Benny ;
Stromgaard, Kristian .
CHEMICAL COMMUNICATIONS, 2009, (25) :3677-3692
[3]   Drug delivery to brain tumors [J].
Blakeley, Jaishri .
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2008, 8 (03) :235-241
[4]   Glioblastoma in adults [J].
Brandes, Alba A. ;
Tosoni, Alicia ;
Franceschi, Enrico ;
Reni, Michele ;
Gatta, Gernma ;
Vecht, Charles .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 67 (02) :139-152
[5]   Second-generation antipsychotics in major depressive disorder: update and clinical perspective [J].
Chen, Jun ;
Gao, Keming ;
Kemp, David E. .
CURRENT OPINION IN PSYCHIATRY, 2011, 24 (01) :10-17
[6]   Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells [J].
Chiu, Chun-Ching ;
Shi, Ya-Fang ;
Yang, Jiann-Jou ;
Hsiao, Yuan-Chao ;
Tzang, Bor-Show ;
Hsu, Tsai-Ching .
PLOS ONE, 2014, 9 (09)
[7]   Application of the Gradient Boosted method in randomised clinical trials: Participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo [J].
Dodd, Seetal ;
Berk, Michael ;
Kelin, Katarina ;
Zhang, Qianyi ;
Eriksson, Elias ;
Deberdt, Walter ;
Nelson, J. Craig .
JOURNAL OF AFFECTIVE DISORDERS, 2014, 168 :284-293
[8]   The paradox of autophagy and its implication in cancer etiology and therapy [J].
Eisenberg-Lerner, Avital ;
Kimchi, Adi .
APOPTOSIS, 2009, 14 (04) :376-391
[9]   Tumour-cell invasion and migration: Diversity and escape mechanisms [J].
Friedl, P ;
Wolf, K .
NATURE REVIEWS CANCER, 2003, 3 (05) :362-374
[10]   CONTROL OF CELL LOCOMOTION - PERTURBATION WITH AN ANTIBODY DIRECTED AGAINST SPECIFIC GLYCOPROTEINS [J].
GOODMAN, SL ;
VOLLMERS, HP ;
BIRCHMEIER, W .
CELL, 1985, 41 (03) :1029-1038