Nardostachys chinensis induces the differentiation of human promyelocytic leukemic cells through the activation of the protein kinase C-dependent extracellular signal-regulated kinase signaling pathway

Ju,Sung-Min; Kang,Jun-Gue; Pae,Hyun-Ock; Lee,Guem-San; Kim,Won-Sin; Lyu,Yeoung-Su; Jeon,Byung-Hun

doi:10.3892/ijmm.2013.1596

Nardostachys chinensis induces the differentiation of human promyelocytic leukemic cells through the activation of the protein kinase C-dependent extracellular signal-regulated kinase signaling pathway

Authors:
- Sung-Min Ju
- Jun-Gue Kang
- Hyun-Ock Pae
- Guem-San Lee
- Won-Sin Kim
- Yeoung-Su Lyu
- Byung-Hun Jeon
View Affiliations

Affiliations: Department of Pathology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea, Department of Microbiology and Immunology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea, Department of Herbology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea, Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea, Department of Neuropsychiatry, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea
Published online on: December 19, 2013 https://doi.org/10.3892/ijmm.2013.1596
Pages: 573-580

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

The underground parts of Nardostachys chinensis (N. chinensis), which belongs the genus Valerianaceae, have been used as sedative and analgesic agents in traditional Korean medicine for centuries. The mitogen‑activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. Protein kinase C (PKC) plays a key role in the regulation of proliferation and differentiation. In this study, we investigated the signaling pathways involved in the differentiation of the HL-60 human leukemic cells induced by N. chinensis extract. Treatment with N. chinensis extract resulted in the activation of the extracellular signal‑regulated kinase (ERK) pathway and induced the differentiation of HL-60 cells into granulocytes. The activation of p38 MAPK was also observed 24 h after treatment; however, the activation of c-Jun N-terminal kinase (JNK) was unaffected. Treatment with an inhibitor of ERK (PD98059) blocked the nitrotetrazolium blue chloride (NBT) reducing activity and CD11b expression in the N. chinensis-treated HL-60 cells, whereas treatment with an inhibitor of p38 MAPK (SB203580) had no significant effect on NBT reducing activity and CD11b expression. In addition, N. chinensis extract increased PKC activity and the protein levels of PKCα, PKCβI and PKCβII isoforms, without a significant change in the protein levels of the PKCγ isoform. PKC inhibitors (GF 109203X, chelerythrine and H-7) inhibited the differentiation of HL-60 cells into granulocytes, as well as ERK activation in the N. chinensis-treated HL-60 cells. These results indicate that the PKC and ERK signaling pathways may be involved in the induction, by N. chinensis extract, of the differentiation of HL-60 cells into granulocytes.

View Figures

View References

1	Seo BI, Lee JH, Choi HY, Kwon DY and Boo YM: Korean Medicine Herbology. Younglim Press; Seoul: pp. 496–497. 2008
2	Xiao PG, Li DP and Yang SL: Modern Chinese Materia Medica. Chemical Industry Press; Beijing: pp. 2522002
3	Takaya Y, Takeuji Y, Akasaka M, et al: Novel guaiane endoperoxides, nardoguaianone A–D, from Nardostachys chinensis roots and their antinociceptive and antimalarial activities. Tetrahedron. 56:7683–7678. 2000.
4	Itokawa H, Masuyama K, Morita H and Takeya K: Cytotoxic sesquiterpenes from Nardostachys chinensis. Chem Pharm Bull (Tokyo). 41:1183–1184. 1993. View Article : Google Scholar
5	Li P, Matsunaga K, Yamamoto K, Yoshikawa R, Kawashima K and Ohizumi Y: Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells. Neurosci Lett. 273:53–56. 1999. View Article : Google Scholar : PubMed/NCBI
6	Hwang JS, Lee SA, Hong SS, et al: Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages. Bioorg Med Chem Lett. 22:706–708. 2012.
7	Huberman E and Callaham MF: Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci USA. 76:1293–1297. 1979. View Article : Google Scholar : PubMed/NCBI
8	Rovera G, Santoli D and Damsky C: Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci USA. 76:2779–2783. 1979. View Article : Google Scholar : PubMed/NCBI
9	Collins SJ, Ruscetti FW, Gallagher RE and Gallo RC: Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA. 75:2458–2462. 1978. View Article : Google Scholar
10	Pan Q, Granger J, O’Connell TD, Somerman MJ and Simpson RU: Promotion of HL-60 cell differentiation by 1,25-dihydroxyvitamin D3 regulation of protein kinase C levels and activity. Biochem Pharmacol. 54:909–915. 1997. View Article : Google Scholar : PubMed/NCBI
11	Kharbanda S, Saleem A, Emoto Y, Stone R, Rapp U and Kufe D: Activation of Raf-1 and mitogen-activated protein kinases during monocytic differentiation of human myeloid leukemia cells. J Biol Chem. 269:872–878. 1994.PubMed/NCBI
12	Kim SH, Oh SM and Kim TS: Induction of human leukemia HL-60 cell differentiation via a PKC/ERK pathway by helenalin, a pseudoguainolide sesquiterpene lactone. Eur J Pharmacol. 511:89–97. 2005. View Article : Google Scholar : PubMed/NCBI
13	Kim SH, Kim HJ and Kim TS: Differential involvement of protein kinase C in human promyelocytic leukemia cell differentiation enhanced by artemisinin. Eur J Pharmacol. 482:67–76. 2003. View Article : Google Scholar : PubMed/NCBI
14	Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M and Lord JM: Serine/threonine protein kinases and apoptosis. Exp Cell Res. 256:34–41. 2000. View Article : Google Scholar : PubMed/NCBI
15	Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K and Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 22:153–183. 2001.PubMed/NCBI
16	Cobb MH: MAP kinase pathways. Prog Biophys Mol Biol. 71:479–500. 1999. View Article : Google Scholar
17	Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270:1326–1331. 1995. View Article : Google Scholar : PubMed/NCBI
18	Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI
19	Yen A, Roberson MS, Varvayanis S and Lee AT: Retinoic acid induced mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase-dependent MAP kinase activation needed to elicit HL-60 cell differentiation and growth arrest. Cancer Res. 58:3163–3172. 1998.
20	Yen A, Roberson MS and Varvayanis S: Retinoic acid selectively activates the ERK2 but not JNK/SAPK or p38 MAP kinases when inducing myeloid differentiation. In Vitro Cell Dev Biol Anim. 35:527–532. 1999. View Article : Google Scholar : PubMed/NCBI
21	Wang X and Studzinski GP: Activation of extracellular signal-regulated kinases (ERKs) defines the first phase of 1,25-dihydroxyvitamin D3-induced differentiation of HL60 cells. J Cell Biochem. 80:471–482. 2001. View Article : Google Scholar : PubMed/NCBI
22	Wang X, Rao J and Studzinski GP: Inhibition of p38 MAP kinase activity up-regulates multiple MAP kinase pathways and potentiates 1,25-dihydroxyvitamin D(3)-induced differentiation of human leukemia HL60 cells. Exp Cell Res. 258:425–437. 2000. View Article : Google Scholar : PubMed/NCBI
23	Wang X and Studzinski GP: Inhibition of p38MAP kinase potentiates the JNK/SAPK pathway and AP-1 activity in monocytic but not in macrophage or granulocytic differentiation of HL60 cells. J Cell Biochem. 82:68–77. 2001. View Article : Google Scholar : PubMed/NCBI
24	Caponigro F, French RC and Kaye SB: Protein kinase C: a worthwhile target for anticancer drugs? Anticancer Drugs. 8:26–33. 1997. View Article : Google Scholar : PubMed/NCBI
25	Nishikawa M and Shirakawa S: The expression and possible roles of protein kinase C in haematopoietic cells. Leuk Lymphoma. 8:201–211. 1992. View Article : Google Scholar : PubMed/NCBI
26	Quest AF: Regulation of protein kinase C: a tale of lipids and proteins. Enzyme Protein. 49:231–261. 1996.PubMed/NCBI
27	Komada F, Nishikawa M, Uemura Y, Morita K, Hidaka H and Shirakawa S: Expression of three major protein kinase C isozymes in various types of human leukemic cells. Cancer Res. 51:4271–4278. 1991.PubMed/NCBI
28	Sakashita A, Nakamaki T, Tsuruoka N, Honma Y and Hozumi M: Granulocyte colony-stimulating factor, not granulocyte-macrophage colony-stimulating factor, co-operates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells. Leukemia. 5:26–31. 1991.
29	Marcinkowska E, Wiedlocha A and Radzikowski C: 1,25-Dihydroxyvitamin D3 induced activation and subsequent nuclear translocation of MAPK is upstream regulated by PKC in HL-60 cells. Biochem Biophys Res Commun. 241:419–426. 1997. View Article : Google Scholar : PubMed/NCBI
30	Breitman TR, Selonick SE and Collins SJ: Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA. 77:2936–2940. 1980. View Article : Google Scholar
31	Tanaka H, Abe E, Miyaura C, Shiina Y and Suda T: 1 alpha,25-dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes. Biochem Biophys Res Commun. 117:86–92. 1983. View Article : Google Scholar : PubMed/NCBI
32	Kang SN, Lee MH, Kim KM, Cho D and Kim TS: Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C. Biochem Pharmacol. 61:1487–1495. 2001. View Article : Google Scholar : PubMed/NCBI