Apoptosis Induced by Glucose-6-phosphate Dehydrogenase Deficiency is Mediated by Caspase-3 and PARP-1 in Human Melanoma Cells

HAO Xiao-Pei,REN Na,TANG Qiong-Lin,ZHANG Chun-Hua,HU Tao,CHEN Long,ZHU Yue-Chun

Chinese Journal of Biochemistry and Molecular Biology ›› 2010, Vol. 26 ›› Issue (12) : 1121-1127.

PDF(580 KB)
PDF(580 KB)
Chinese Journal of Biochemistry and Molecular Biology ›› 2010, Vol. 26 ›› Issue (12) : 1121-1127.
Reviews

Apoptosis Induced by Glucose-6-phosphate Dehydrogenase Deficiency is Mediated by Caspase-3 and PARP-1 in Human Melanoma Cells

  • HAO Xiao-Pei,REN Na,TANG Qiong-Lin,ZHANG Chun-Hua,HU Tao,CHEN Long,ZHU Yue-Chun
Author information +
History +

Abstract

The mechanism of overexpression of glucose-6-phosphate dehydrogenase (G6PD )in many tumor cells, is no still largely understood. To elucidate the relationship between G6PD and human melanoma, human epidermal melanocyte(HEM),human melanoma A375(A375-WT) and G6PD deficient A375 (A375-G6PDΔ) were used to study the development of cell apoptosis and its mechanism. Real-time PCR and Western blotting showed that mRNA and protein of G6PD in A375-WT cells increased by 1.89 times(P<0.05) and 6.86 times(P<0.01), respectively, with 2.30 times (P<0.05) increase of G6PD activity, as those of HEM cells. Further study showed that a apoptotic rate increased by 5.10-fold (P<0.01) in A375-G6PDΔ cells with annexin V/PI flow cytometry analysis, and cleaved caspase-3 and 89 kD PARP-1 raised by 1.84-fold, 2.87-fold, respectively. In addition, A375-G6PDΔ cells showed that levels of NADPH and GSH decreased by 72.30%(P<0.01), 27.39%(P<0.05), respectively, with 75.43% increase of H2O2 (P<0.01), as those of A375-WT cells. These results suggest that the apoptosis induced by G6PD deficiency may be mediated by caspase-3 and PARP-1 in human melanoma cells, which may be a new clue in the study of melanoma tumorigenesis.

Key words

glucose-6-phosphate dehydrogenase / melanoma / Caspase-3 / PARP-1 / cell apoptosis

Cite this article

Download Citations
HAO Xiao-Pei,REN Na,TANG Qiong-Lin,ZHANG Chun-Hua,HU Tao,CHEN Long,ZHU Yue-Chun. Apoptosis Induced by Glucose-6-phosphate Dehydrogenase Deficiency is Mediated by Caspase-3 and PARP-1 in Human Melanoma Cells[J]. Chinese Journal of Biochemistry and Molecular Biology, 2010, 26(12): 1121-1127

References

[1]   Lens M B, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma[J]. Br J Dermatol, 2004,150(2):179-185 [2]   Garbe C, Eigentler T K. Diagnosis and treatment of cutaneous melanoma: state of the art 2006[J]. Melanoma Res, 2007,17(2): 117–127 [3]   Pop C, Salvesen G S. Human caspases: activation, specificity, and regulation [J]. J Biol Chem, 2009, 284(33): 21777-21781 [4]   Denault J B, Salvesen G S. Apoptotic caspase activation and activity [J]. Methods Mol Biol, 2008, 414: 191-220 [5]   Kim D S, Jeon S E, Jeong Y M, et al. Hydrogen peroxide is a mediator of indole-3-acetic acid/horseradish peroxidase-induced apoptosis[J]. FEBS Lett, 2006, 580(5):1439-1446 [6]   Li D Y, Zhu Y, Tang Q L, et al. A new G6PD knockdown tumor-cell line with reduced proliferation and increased susceptibility to oxidative stress[J]. Cancer Biother Radiopharm, 2009, 24(1): 81-90 [7]   朱月春,吕会茹,李丹怡,等. siRNA沉默G6PD表达对人皮肤黑色素瘤细胞生长及凋亡的影响[J]. 生物化学与生物物理进展(Zhu Yue-Chun, Lv Hui-Ru, Li Dan-Yi, et al. Effects of silencing G6PD expression on the growth and apoptosis in human skin melanoma[J]. Prog Biochem Biophys), 2008, 35(3): 327-334 [8]   李媛,王新文,金岩,等.组织工程皮肤中黑色素细胞的培养纯化[J]. 中国临床康复 (Li Yuan, Wang Xin-Wen, Jin Yan, et al. Isolation of pure skin melanocytes[J]. Chin J Clin Rehabil), 2002, 6(24): 3697,3705 [9]   卢涛,刘源,金岩,等. 两段法培养适合临床移植应用的黑素细胞的安全性研究[J]. 中国临床康复( Lu Tao, Liu Yuan, Jin Yan, et al. Security of human melanocytes cultured by two step method[J].Chin J Clin Rehabil), 2004, 8(17): 3242-3244 [10]   Yang Y F, Zhu Y C, Li D Y, et al. Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the A Chang population of southwestern China[J]. Sci China Ser C-Life, 2007,50(4):479-485 [11]   Furuta E, Okuda H, Kobayashi A, et al. Metabolic genes in cancer: their roles in tumor progression and clinical implications[J]. Biochim Biophys Acta, 2010, 1805(2):141-152 [12]   Ohl F, Jung M, Radoni A, et al. Identification and validation of suitable endogenous reference genes for gene expression studies of human bladder cancer[J]. J Urol, 2006, 175(5): 1915-1920 [13]   Ohl F,Jung M, Xu C, et al. Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization[J]. J Mol Med, 2005, 83(12): 1014–1024 [14]   Langbein S, Frederiks W M, zur Hausen A, et al. Metastasis is promoted by a bioenergetic switch: New targets for progressive renal cell cancer[J]. Int J Cancer, 2008, 121(11): 2422–2428 [15]   Kekec Y, Paydas S, Tuli A, et al. Antioxidant enzyme levels in cases with gastrointesinal cancer[J]. Eur J Intern Med, 2009, 20(4): 403-406 [16]   Murtas D, Piras F. Nuclear 8-hydroxy-2′-deoxyguanosine as survival biomarker in patients with cutaneous melanoma[J]. Oncol Rep, 2010, 23(2): 329-335 [17]   Starcevic S L, Diotte N M, Zukowski K L, et al. Oxidative DNA damage and repair in a cell lineage model of human proliferative breast disease (PBD) [J].Toxicol Sci, 2003, 75(1): 74-81 [18]   Nguewa P A, Fuertes M A, Valladares B, et al. Poly(ADP-ribose) polymerases: homology, structure domains and functions. Novel therapeutical applications[J]. Prog Biophys Mol Biol, 2005, 88(1): 143-172 [19]   Lin R J, Cheng M J, Huang J C, et al. Cytotoxic compounds from the stems of Cinnamomum tenuifolium[J]. J Nat Prod, 2009,72(10): 1816-1824 [20]   Koh D W, Dawson T M, Dawson V L. Mediation of cell death by poly(ADP-ribose) polymerase-1[J]. Pharmacol Res, 2005, 52(1): 5-14 [21]   Ahmad K A, Wang G, Ahmed K. Intracellular hydrogen peroxide production is an upstream event in apoptosis induced by down-regulation of casein kinase 2 in prostate cancer cells[J]. Mol Cancer Res, 2006, 4(5): 331-338

Funding

National Natural Science Foundation of China (No.30460049, 30860322) and Yunnan Provincial Science and Technology Foundation (No. 2007PY 01-13)

PDF(580 KB)

146

Accesses

0

Citation

Detail

Sections
Recommended

/