NDRG1 is down-regulated in the early apoptotic event induced by camptothecin analogs: The potential role in proteolytic activation of PKCδ and apoptosis
Ying Zheng
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorLi-Shun Wang
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorLi Xia
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorYu-Hui Han
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorShi-Hua Liao
Division of Functional Genomics of Cancer, Institute of Health Science, SJTU-SM/Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorXiao-Ling Wang
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorJin-Ke Cheng Dr.
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Additional corresponding author
Search for more papers by this authorCorresponding Author
Guo-Qiang Chen Dr.
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Division of Functional Genomics of Cancer, Institute of Health Science, SJTU-SM/Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, No 280, Chong-Qing South Road, Shanghai 200025, China Fax: +86-21-6415-4900===Search for more papers by this authorYing Zheng
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorLi-Shun Wang
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorLi Xia
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorYu-Hui Han
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorShi-Hua Liao
Division of Functional Genomics of Cancer, Institute of Health Science, SJTU-SM/Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorXiao-Ling Wang
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Search for more papers by this authorJin-Ke Cheng Dr.
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Additional corresponding author
Search for more papers by this authorCorresponding Author
Guo-Qiang Chen Dr.
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China
Division of Functional Genomics of Cancer, Institute of Health Science, SJTU-SM/Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, No 280, Chong-Qing South Road, Shanghai 200025, China Fax: +86-21-6415-4900===Search for more papers by this authorAbstract
We previously reported that NSC606985, a new camptothecin analog, induces apoptosis of acute myeloid leukemic cells, which is triggered by proteolytic activation of protein kinase C delta (PKCδ). Here, we performed quantitative proteomic analysis of NSC606985-treated and untreated leukemic U937 cells with two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) in combination with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry. Thirty-three proteins were found to be deregulated. Then, we focused on N-myc downstream regulated gene 1 (NDRG1) down-regulated during apoptosis induction. The results demonstrated that the down-regulation of NDRG1 protein but not its mRNA was an early event prior to proteolytic activation of PKCδ in U937 cells under treatments of NSC606985 as well as other camptothecin analogs. With the ectopic expression of NDRG1, the proteolytic activation of PKCδ in NSC606985-treated leukemic cells was delayed and the cells were less sensitive to apoptosis. On the contrary, the suppression of NDRG1 expression by specific small interfering RNA significantly enhanced NSC606985-induced activation of PKCδ and apoptosis of U937 cells. In summary, our study suggests that the down-regulation of NDRG1 is involved in proteolytic activation of PKCδ during apoptosis induction, which would shed new light on the understanding the apoptotic process initiated by camptothecin.
References
- 1
Raff, M. C.,
Social controls on cell survival and cell death.
Nature
1992,
356,
397–400.
- 2
Vermeulen, K.,
Van Bockstaele, D. R.,
Berneman, Z. N.,
Apoptosis: mechanisms and relevance in cancer.
Ann. Hematol.
2005,
84,
627–639.
- 3
Havelka, A. M.,
Berndtsson, M.,
Olofsson, M. H.,
Shoshan, M. C.,
Linder, S.,
Mechanisms of action of DNA-damaging anticancer drugs in treatment of carcinomas: is acute apoptosis an “off-target” effect?
Mini Rev. Med. Chem.
2007,
7,
1035–1039.
- 4
Riedl, S. J.,
Shi, Y.,
Molecular mechanisms of caspase regulation during apoptosis.
Nat. Rev. Mol. Cell. Biol.
2004,
5,
897–907.
- 5
Nunez, G.,
Benedict, M. A.,
Hu, Y.,
Inohara, N.,
Caspases: the proteases of the apoptotic pathway.
Oncogene
1998,
17,
3237–3245.
- 6
Livneh, E.,
Fishman, D. D.,
Linking protein kinase C to cell-cycle control.
Eur. J. Biochem.
1997,
248,
1–9.
- 7
Watanabe, T.,
Ono, Y.,
Taniyama, Y.,
Hazama, K. et al.,
Cell division arrest induced by phorbol ester in CHO cells overexpressing protein kinase C-delta subspecies.
Proc. Natl. Acad. Sci. USA
1992,
89,
10159–10163.
- 8
Emoto, Y.,
Manome, Y.,
Meinhardt, G.,
Kisaki, H. et al.,
Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells.
EMBO J.
1995,
14,
6148–6156.
- 9
Mizuno, K.,
Noda, K.,
Araki, T.,
Imaoka, T. et al.,
The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-O-tetradecanoyl-phorbol-13-acetate-induced apoptosis.
Eur. J. Biochem.
1997,
250,
7–18.
- 10
Denning, M. F.,
Wang, Y.,
Nickoloff, B. J.,
Wrone-Smith, T.,
Protein kinase C delta is activated by caspase-dependent proteolysis during ultraviolet radiation-induced apoptosis of human keratinocytes.
J. Biol. Chem.
1998,
273,
29995–30002.
- 11
Reyland, M. E.,
Anderson, S. M.,
Matassa, A. A.,
Barzen, K. A.,
Quissell, D. O.,
Protein kinase C delta is essential for etoposide-induced apoptosis in salivary gland acinar cells.
J. Biol. Chem.
1999,
274,
19115–19123.
- 12
Basu, A.,
Woolard, M. D.,
Johnson, C. L.,
Involvement of protein kinase C delta in DNA damage-induced apoptosis.
Cell Death Differ.
2001,
8,
899–908.
- 13
Yoshida, K.,
PKCdelta signaling: mechanisms of DNA damage response and apoptosis.
Cell. Signal.
2007,
19,
892–901.
- 14
Basu, A.,
Akkaraju, G. R.,
Regulation of caspase activation and cis-diamminedichloroplatinum(II)-induced cell death by protein kinase C.
Biochemistry
1999,
38,
4245–4251.
- 15
Song, M. G.,
Gao, S. M.,
Du, K. M.,
Xu, M. et al.,
Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase C delta-dependent mechanisms.
Blood
2005,
105,
3714–3721.
- 16
Leverrier, S.,
Vallentin, A.,
Joubert, D.,
Positive feedback of protein kinase C proteolytic activation during apoptosis.
Biochem. J.
2002,
368,
905–913.
- 17
Blass, M.,
Kronfeld, I.,
Kazimirsky, G.,
Blumberg, P. M.,
Brodie, C.,
Tyrosine phosphorylation of protein kinase C delta is essential for its apoptotic effect in response to etoposide.
Mol. Cell. Biol.
2002,
22,
182–195.
- 18
Anantharam, V.,
Kitazawa, M.,
Wagner, J.,
Kaul, S.,
Kanthasamy, A. G.,
Caspase-3-dependent proteolytic cleavage of protein kinase C delta is essential for oxidative stress-mediated dopaminergic cell death after exposure to methylcyclopentadienyl manganese tricarbonyl.
J. Neurosci.
2002,
22,
1738–1751.
- 19
Tonge, R.,
Shaw, J.,
Middleton, B.,
Rowlinson, R. et al.,
Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology.
Proteomics
2001,
1,
377–396.
- 20
Han, Y. H.,
Xia, L.,
Song, L. P.,
Zheng, Y. et al.,
Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells.
Proteomics
2006,
6,
3262–3274.
- 21
Boer, J.,
Bonten-Surtel, J.,
Grosveld, G.,
Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis.
Mol. Cell. Biol.
1998,
18,
1236–1247.
- 22
Stein, S.,
Thomas, E. K.,
Herzog, B.,
Westfall, M. D. et al.,
NDRG1 is necessary for p53-dependent apoptosis.
J. Biol. Chem.
2004,
279,
48930–48940.
- 23
Chen, B.,
Nelson, D. M.,
Sadovsky, Y.,
N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury.
J. Biol. Chem.
2006,
281,
2764–2772.
- 24
Zhao, K. W.,
Li, X.,
Zhao, Q.,
Huang, Y. et al.,
Protein kinase C delta mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation.
Blood
2004,
104,
3731–3738.
- 25
Yan, H.,
Wang, Y. C.,
Li, D.,
Wang, Y. et al.,
Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase C delta.
Leukemia
2007,
21,
1488–1495.
- 26
Carie, A. E.,
Sebti, S. M.,
A chemical biology approach identifies a beta-2 adrenergic receptor agonist that causes human tumor regression by blocking the Raf-1/Mek-1/Erk1/2 pathway.
Oncogene
2007.
- 27
Huang, Z.,
The chemical biology of apoptosis. Exploring protein-protein interactions and the life and death of cells with small molecules.
Chem. Biol.
2002,
9,
1059–1072.
- 28
Thiede, B.,
Rudel, T.,
Proteome analysis of apoptotic cells.
Mass Spectrom. Rev.
2004,
23,
333–349.
- 29
Machuy, N.,
Thiede, B.,
Rajalingam, K.,
Dimmler, C. et al.,
A global approach combining proteome analysis and phenotypic screening with RNA interference yields novel apoptosis regulators.
Mol. Cell. Proteomics
2005,
4,
44–55.
- 30
Yu, Y.,
Wang, L. S.,
Shen, S. M.,
Xia, L. et al.,
Subcellular proteome analysis of camptothecin analogue NSC606985-treated acute myeloid leukemic cells.
J. Proteome Res.
2007,
6,
3808–3818.
- 31
van Belzen, N.,
Dinjens, W. N.,
Diesveld, M. P.,
Groen, N. A. et al.,
A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms.
Lab. Invest.
1997,
77,
85–92.
- 32
Zhou, D.,
Salnikow, K.,
Costa, M.,
Cap43, a novel gene specifically induced by Ni2+ compounds.
Cancer Res.
1998,
58,
2182–2189.
- 33
Kurdistani, S. K.,
Arizti, P.,
Reimer, C. L.,
Sugrue, M. M. et al.,
Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage.
Cancer Res.
1998,
58,
4439–4444.
- 34
Park, H.,
Adams, M. A.,
Lachat, P.,
Bosman, F. et al.,
Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and malignant cells.
Biochem. Biophys. Res. Commun.
2000,
276,
321–328.
- 35
Kokame, K.,
Kato, H.,
Miyata, T.,
Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes.
J. Biol. Chem.
1996,
271,
29659–29665.
- 36
Lachat, P.,
Shaw, P.,
Gebhard, S.,
van Belzen, N. et al.,
Expression of NDRG1, a differentiation-related gene, in human tissues.
Histochem. Cell. Biol.
2002,
118,
399–408.
- 37
Kovacevic, Z.,
Richardson, D. R.,
The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer.
Carcinogenesis
2006,
27,
2355–2366.
- 38
Motwani, M.,
Sirotnak, F. M.,
She, Y.,
Commes, T.,
Schwartz, G. K.,
Drg1, a novel target for modulating sensitivity to CPT-11 in colon cancer cells.
Cancer Res.
2002,
62,
3950–3955.
- 39
Shiohara, M.,
Akashi, M.,
Gombart, A. F.,
Yang, R.,
Koeffler, H. P.,
Tumor necrosis factor alpha: posttranscriptional stabilization of WAF1 mRNA in p53-deficient human leukemic cells.
J. Cell. Physiol.
1996,
166,
568–576.
