Epigallocatechin‑3‑gallate induces apoptosis in acute promyelocytic leukemia cells via a SHP‑1‑p38α MAPK‑Bax cascade

Gan,Liugen; Zhong,Liang; Shan,Zhiling; Xiao,Chunlan; Xu,Ting; Song,Hao; Li,Liu; Yang,Rong; Liu,Beizhong

doi:10.3892/ol.2017.6980

Epigallocatechin‑3‑gallate induces apoptosis in acute promyelocytic leukemia cells via a SHP‑1‑p38α MAPK‑Bax cascade

Authors:
- Liugen Gan
- Liang Zhong
- Zhiling Shan
- Chunlan Xiao
- Ting Xu
- Hao Song
- Liu Li
- Rong Yang
- Beizhong Liu
View Affiliations

Affiliations: Central Laboratory, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Faculty of Laboratory Medical, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/ol.2017.6980
Pages: 6314-6320

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acute promyelocytic leukemia (APL) is characterized by a specific chromosomal translation, resulting in a fusion gene that affects the differentiation, proliferation and apoptosis of APL cells. Epigallocatechin‑3‑gallate (EGCG), a catechin, exhibits numerous biological functions, including antitumor activities. Previous studies have reported that EGCG induces apoptosis in NB4 cells. However, the molecular mechanism underlying EGCG‑induced apoptosis remains unclear. The present study aimed to determine the molecular basis of EGCG‑induced apoptosis in NB4 cells. EGCG treatment significantly inhibited the viability of NB4 cells in a dose‑dependent manner. In addition, EGCG treatment induced apoptosis and increased the levels of (Bcl‑2‑like protein 4) Bax protein expression. Moreover, EGCG treatment was able to increase phosphorylated (p)‑p38α mitogen‑activated protein kinase (MAPK) and Src homology 1 domain‑containing protein tyrosine phosphatase (SHP‑1) expression. Pretreatment with PD169316 (a p38 MAPK inhibitor) partially blocked EGCG‑induced apoptosis and inhibited EGCG‑mediated Bax expression. Similarly, pretreatment with NSC87877, an inhibitor of SHP‑1, partially blocked EGCG‑induced apoptosis and inhibited EGCG‑mediated increases in p‑p38α MAPK and Bax expression. Therefore, the results of the present study indicate that EGCG is able to induce apoptosis in NB4 cells via the SHP‑1‑p38αMAPK‑Bax cascade.

View Figures

View References

1	de Thé H, Le Bras M and Lallemand-Breitenbach V: The cell biology of disease: Acute promyelocytic leukemia, arrsenic, and PML bodies. J Cell Biol. 198:11–21. 2012. View Article : Google Scholar : PubMed/NCBI
2	Laurenzana A, Pettersson F and Miller WH: Role of PML/RARAα in the pathogenesis of APL. Drug Discov Today Dis Mech. 3:499–505. 2006. View Article : Google Scholar
3	Congleton J, MacDonald R and Yen A: Src inhibitors, PP2 and dasatinib, increase retinoic acid-induced association of Lyn and c-Raf (S259) and enhance MAPK-dependent differentiation of myeloid leukemia cells. Leukemia. 26:1180–1188. 2012. View Article : Google Scholar : PubMed/NCBI
4	Liang H, Li X, Wang L, Yu S, Xu Z, Gu Y, Pan Z, Li T, Hu M, Cui H, et al: MicroRNAs contribute to promyelocyte apoptosis in As2O3-treated APL cells. Cell Physiol Biochem. 32:1818–1829. 2013. View Article : Google Scholar : PubMed/NCBI
5	Petrie K, Zelent A and Waxman S: Differentiation therapy of acute myeloid leukemia: Past, present and future. Curr Opin Hematol. 16:84–91. 2009. View Article : Google Scholar : PubMed/NCBI
6	Neel BG, Gu H and Pao L: The “Shp”ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 28:284–293. 2003. View Article : Google Scholar : PubMed/NCBI
7	Stocco DR and Shen SH: Human protein tyrosine phosphatase 1C (PTPN6) gene structure: Alternate promoter usage and exon skipping generate multiple transcripts. Genomics. 27:165–173. 1995. View Article : Google Scholar : PubMed/NCBI
8	Tseng CYLM, Su JC, Chang KC, Chu PY, Tai WT, Shiau CW and Chen KF: Novel sorafenib analogues induces apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells. Breast Cancer Res. 15:R632013.PubMed/NCBI
9	Dong G, You M, Ding L, Fan H, Liu F, Ren D and Hou Y: STING negatively regulates Double-Stranded DNA-activated JAK1-STAT1 signaling via SHP-1/2 in B cells. Mol Cells. 38:441–451. 2015. View Article : Google Scholar : PubMed/NCBI
10	Al-Jamal HA, Jusoh Mat SA, Hassan R and Johan MF: Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia. BMC Canner. 15:8692015. View Article : Google Scholar
11	Xiong A, Yu W, Liu Y, Sanders BG and Kline K: Elimination of ALDH+ breast tumor initiating cells by docosahexanoic acid and/or gamma tocotrienol through SHP-1 inhibition of Stat3 signaling. Mol Carcinog. 55:420–430. 2016. View Article : Google Scholar : PubMed/NCBI
12	Fan LC, Teng HW, Shiau CW, Lin H, Hung MH, Chen YL, Huang JW, Tai WT, Yu HC and Chen KF: SHP-1 is a target of regorafenib in colorectal cancer. Oncatarget. 5:6243–6251. 2014. View Article : Google Scholar
13	Nakase K, Cheng J, Zhu Q and Marasco WA: Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells. J Leukoc Biol. 85:165–174. 2009. View Article : Google Scholar : PubMed/NCBI
14	Delibrias CC, Floettmann JE, Rowe M and Fearon DT: Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes. J Exp Med. 186:1575–1583. 1997. View Article : Google Scholar : PubMed/NCBI
15	Uesugi Y, Fuse I, Toba K, Kishi K, Furukawa T, Koike T and Aizawa Y: Involvement of SHP-1, a phosphotyrosine phosphatase, during myeloid cell differentiation in acute promyelocytic leukemia cell lines. Eur J Haematol. 62:239–245. 1999. View Article : Google Scholar : PubMed/NCBI
16	Amin HM, Hoshino K, Yang H, Lin Q, Lai R and Garcia-Manero G: Decreased expression level of SH2 domain-containing protein tyrosine phosphatase-1 (Shp1) is associated with progression of chronic myeloid leukaemia. J Pathol. 212:402–410. 2007. View Article : Google Scholar : PubMed/NCBI
17	Nakazato T, Ito K, Miyakawa Y, Kinjo K, Yamada T, Hozumi N, Ikeda Y and Kizaki M: Catechin, a green tea component, rapidly induces apoptosis of myeloid leukemia cells via modulation of reactive oxygen species production in vitro andinhibits tumor growth in vivo. Haematologica. 90:317–325. 2005.PubMed/NCBI
18	Britschgi A, Simon HU, Tobler A, Fey MF and Tschan MP: Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2. Br J Haematol. 149:55–64. 2010. View Article : Google Scholar : PubMed/NCBI
19	Jung JH, Yun M, Choo EJ, Kim SH, Jeong MS, Jung DB, Lee H, Kim EO, Kato N, Kim B, et al: A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia. Br J Pharmacol. 172:3565–3578. 2015. View Article : Google Scholar : PubMed/NCBI
20	Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, Aiello LP, Kern TS and King GL: Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med. 15:1298–1306. 2009. View Article : Google Scholar : PubMed/NCBI
21	Harsha Raj M, Yashaswini B, Rössler J and Salimath BP: Combinatorial treatment with anacardic acid followed by TRAIL augments induction of apoptosis in TRAIL resistant cancer cells by the regulation of p53, MAPK and NFκβ pathways. Apoptosis. 21:578–593. 2016. View Article : Google Scholar : PubMed/NCBI
22	Zhang JG, Yang S, Qiao J, Li T, Yang S and Hong Y: Macrophage migration inhibitory factor regulating the expression of VEGF-C through MAPK signal pathways in breast cancer MCF-7 cell. World J Surg Oncol. 14:512016. View Article : Google Scholar : PubMed/NCBI
23	Rodríguez-Berriguete G, Torrealba N, Fraile B, Paniagua R and Royuela M: Epidermal growth factor induces p38 MAPK-dependent G0/G1-to-S transition in prostate cancer cells upon androgen deprivation conditions. Growth Factor. 34:5–10. 2016. View Article : Google Scholar
24	Mandegary A, Hosseini R, Ghaffari SH, Alimoghaddam K, Rostami S, Ghavamzadeh A and Ghahremani MH: The expression of p38, ERK1 and Bax proteins has increased during the treatment of newly diagnosed acute promyelocytic leukemia with arsenic trioxide. Ann Oncol. 21:1884–1890. 2010. View Article : Google Scholar : PubMed/NCBI
25	Tyurin VA, Balasubramanian K, Winnica D, Tyurina YY, Vikulina AS, He RR, Kapralov AA, Macphee CH and Kagan VE: Oxidatively modified phosphatidylserines om the surface of apoptotic cells are essential phagocytic ‘eat-me’ signals: Cleavage and inhibition of phagocytosis by Lp-PLA2. Cell Death Differ. 21:825–835. 2014. View Article : Google Scholar : PubMed/NCBI
26	Toden S, Tran HM, Tovar-Camargo OA, Okugawa Y and Goel A: Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer. Oncotarget. 7:16158–16171. 2016. View Article : Google Scholar : PubMed/NCBI
27	Li M, Li JJ, Gu QH, An J, Cao LM, Yang HP and Hu CP: EGCG induces lunch canner A549 cells apoptosis by regulating Ku70 acetylation. Oncol Rep. 35:2339–2347. 2016. View Article : Google Scholar : PubMed/NCBI
28	Tofolean IT, Ganea C, Ionescu D, Filippi A, Garaiman A, Goicea A, Gaman MA, Dimancea A and Baran I: Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells. Pharmacol Res. 103:300–317. 2016. View Article : Google Scholar : PubMed/NCBI
29	Vézina A, Chokor R and Annabi B: EGCG targeting efficacy of NF-κB downstream gene products is dictated by the monocytic/macrophagic differentiation status of promyelocytic leukemia cells. Cancer Immunol Immunother. 16:2321–2331. 2012. View Article : Google Scholar
30	Elbling L, Herbacek I, Weiss RM, Jantschitsch C, Micksche M, Gerner C, Pangratz H, Grusch M, Knasmüller S and Berger W: Hydrogen peroxide mediates EGCG-induced antioxidant protection in human keratinocytes. Free Radic Biol Med. 49:1444–1452. 2010. View Article : Google Scholar : PubMed/NCBI
31	Khan TH, Srivastava N, Srivastava A, Sareen A, Mathur RK, Chande AG, Musti KV, Roy S, Mukhopadhyaya R and Saha B: SHP-1 plays a crucial role in CD40 signaling reciprocity. J Immunol. 193:3644–3653. 2014. View Article : Google Scholar : PubMed/NCBI
32	Chen YY, Hsieh CY, Jayakumar T, Lin KH, Chou DS, Lu WJ, Hsu MJ and Sheu JR: Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade. Sci Rep. 4:56512014. View Article : Google Scholar : PubMed/NCBI