Curcumin Induces Apoptosis of Upper Aerodigestive Tract Cancer Cells by Targeting Multiple Pathways

被引:31
作者
Amin, A. R. M. Ruhul [1 ]
Haque, Abedul [1 ]
Rahman, Mohammad Aminur [1 ]
Chen, Zhuo Georgia [1 ]
Khuri, Fadlo Raja [1 ]
Shin, Dong Moon [1 ]
机构
[1] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA
来源
PLOS ONE | 2015年 / 10卷 / 04期
关键词
BCL-2; INHIBITION; P53; PERSPECTIVES; INDUCTION; GROWTH; ASSAY;
D O I
10.1371/journal.pone.0124218
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2.
引用
收藏
页数:11
相关论文
共 30 条
[1]   A novel role for p73 in the regulation of Akt-Foxo1a-Bim signaling and apoptosis induced by the plant lectin, concanavalin A [J].
Amin, A. R. M. Ruhul ;
Paul, Rajib K. ;
Thakur, Vijay S. ;
Agarwal, Munna L. .
CANCER RESEARCH, 2007, 67 (12) :5617-5621
[2]   SHP-2 tyrosine phosphatase inhibits p73-dependent apoptosis and expression of a subset of p53 target genes induced by EGCG [J].
Amin, A. R. M. Ruhul ;
Thakur, Vijay S. ;
Paul, Rajib K. ;
Feng, Gen Sheng ;
Qu, Cheng-Kui ;
Mukhtar, Hasan ;
Agarwal, Munna L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (13) :5419-5424
[3]   N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy [J].
Amin, A. R. M. Ruhul ;
Thakur, V. S. ;
Gupta, K. ;
Agarwal, M. K. ;
Wald, D. N. ;
Shin, D. M. ;
Agarwal, M. L. .
ONCOGENE, 2013, 32 (07) :920-929
[4]   Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (-)-Epigallocatechin-3-gallate and Luteolin POTENTIAL ROLE OF p53 [J].
Amin, A. R. M. Ruhul ;
Wang, Dongsheng ;
Zhang, Hongzheng ;
Peng, Shifang ;
Shin, Hyung Ju C. ;
Brandes, Johann C. ;
Tighiouart, Mourad ;
Khuri, Fadlo R. ;
Chen, Zhuo Georgia ;
Shin, Dong M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (45) :34557-34565
[5]   Perspectives for Cancer Prevention With Natural Compounds [J].
Amin, A. R. M. Ruhul ;
Kucuk, Omer ;
Khuri, Fadlo R. ;
Shin, Dong M. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (16) :2712-2725
[6]  
[Anonymous], COLD SPRING HARB PER
[7]   Cancer Prevention With Natural Compounds [J].
Collett, Norleena P. ;
Amin, A. R. M. Ruhul ;
Bayraktar, Soley ;
Pezzuto, John M. ;
Shin, Dong M. ;
Khuri, Fadlo R. ;
Aggarwal, Bharat B. ;
Surh, Young-Joon ;
Kucuk, Omer .
SEMINARS IN ONCOLOGY, 2010, 37 (03) :258-281
[8]   p63 and p73, the Ancestors of p53 [J].
Doetsch, V. ;
Bernassola, F. ;
Coutandin, D. ;
Candi, E. ;
Melino, G. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2010, 2 (09) :a004887
[9]   PI3K and cancer: lessons, challenges and opportunities [J].
Fruman, David A. ;
Rommel, Christian .
NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (02) :140-156
[10]   The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity [J].
Houghton, Peter ;
Fang, Rui ;
Techatanawat, Isariya ;
Steventon, Glyn ;
Hylands, Peter J. ;
Lee, C. C. .
METHODS, 2007, 42 (04) :377-387