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http://dx.doi.org/10.5352/JLS.2015.25.11.1255

Induction of Apoptosis by Ethanol Extract of Cnidium officinale in Human Leukemia U937 Cells through Activation of AMPK  

Jeong, Jin-Woo (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University)
Publication Information
Journal of Life Science / v.25, no.11, 2015 , pp. 1255-1264 More about this Journal
Abstract
Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.
Keywords
AMPK; apoptosis; Cnidium officinale; U937 cells;
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1 Bae, S. S., Perry, D. K., Oh, Y. S., Choi, J. H., Galadari, S. H., Ghayur, T., Ryu, S. H., Hannun, Y. A. and Suh, P. G. 2000. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells. FASEB J. 14, 1083-1092.
2 Brunelle, J. K. and Letai, A. 2009. Control of mitochondrial apoptosis by the Bcl-2 family. J. Cell Sci. 122, 437-441.   DOI
3 Chen, S., Xiao, X., Feng, X., Li, W., Zhou, N., Zheng, L., Sun, Y., Zhang, Z. and Zhu, W. 2012. Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression. J. Nutr. Biochem. 23, 1100-1112.   DOI
4 de Almagro, M. C. and Vucic, D. 2012. The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp. Oncol. 34, 200-211.
5 de la Cruz, J., Kim, D. H. and Hwang, S. G. 2014. Anti cancer effects of Cnidium officinale Makino extract mediated through apoptosis and cell cycle arrest in the HT-29 human colorectal cancer cell line. Asian Pac. J. Cancer Prev. 15, 5117-5121.   DOI
6 Fiandalo, M. V. and Kyprianou, N. 2012. Caspase control: protagonists of cancer cell apoptosis. Exp. Oncol. 34, 165-175.
7 Fogarty, S. and Hardie, D. G. 2010. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim. Biophys. Acta. 1804, 581-591.   DOI
8 Fukuda, K. 1999. Apoptosis-associated cleavage of beta-catenin in human colon cancer and rat hepatoma cells. Int. J. Biochem. Cell Biol. 31, 519-529.   DOI
9 Fulda, S. and Debatin, K. M. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798-4811.   DOI
10 Han, S. I., Kim, Y. S. and Kim, T. H. 2008. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 41, 1-10.   DOI
11 Hardie, D. G., Hawley, S. A. and Scott, J. W. 2006. AMP-activated protein kinase--development of the energy sensor concept. J. Physiol. 574, 7-15.   DOI
12 Jeong, J. B., Ju, S. Y., Park, J. H., Lee, J. R., Yun, K. W., Kwon, S. T., Lim, J. H., Chung, G. Y. and Jeong, H. J. 2009. Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong Hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell. Cancer Epidemiol. 33, 41-46.   DOI
13 Jin, Z. and El-Deiry, W. S. 2005. Overview of cell death signaling pathways. Cancer Biol. Ther. 4, 139-163.
14 Kwak, D. H., Kim, J. K., Kim, J. Y., Jeong, H. Y., Keum, K. S., Han, S. H., Rho, Y. I., Woo, W. H., Jung, K. Y., Choi, B. K. and Choo, Y. K. 2002. Anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus. J. Ethnopharmacol. 81, 373-379.   DOI
15 Lee, D. H., Lee, T. H., Jung, C. H. and Kim, Y. H. 2012. Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells. Cell. Signal. 24, 2216-2225.   DOI
16 Martinou, J. C. and Youle, R. J. 2011. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev. Cell 21, 92-101.   DOI
17 Lee, S. H., Lee, J. H., Oh, E. Y., Kim, G. Y., Choi, B. T., Kim, C. and Choi, Y. H. 2013. Ethanol extract of Cnidium officinale exhibits anti-inflammatory effects in BV2 microglial cells by suppressing NF-κB nuclear translocation and the activation of the PI3K/Akt signaling pathway. Int. J. Mol. Med. 32, 876-882.
18 Li, H., Zhu, H., Xu, C. J. and Yuan, J. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501   DOI
19 Lopez-Beltran, A., Maclennan, G. T., de la Haba-Rodriguez, J., Montironi, R. and Cheng, L. 2007. Research advances in apoptosis-mediated cancer therapy: a review. Anal. Quant. Cytol. Histol. 29, 71-78.
20 Momcilovic, M., Hong, S. P. and Carlson, M. 2006. Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J. Biol. Chem. 281, 25336-25343.   DOI
21 Okada, H. and Mak, T. W. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 4, 592-603.   DOI
22 Ozaki, Y., Sekita, S. and Harada, M. 1989. Centrally acting muscle relaxant effect of phthalides (ligustilide, cnidilide and senkyunolide) obtained from Cnidium officinale Makino. Yakugaku Zasshi 109, 402-406.
23 Peter, M. E. and Krammer, P. H. 2003. The CD95 (APO-1/Fas) DISC and beyond. Cell Death Differ. 10, 26-35.   DOI
24 Shen, Q. W., Zhu, M. J., Tong, J., Ren, J. and Du, M. 2007. Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha-lipoic acid in C2C12 myotubes. Am. J. Physiol. Cell Physiol. 293, C1395-1403.   DOI
25 Wu, S. J., Huang, G. Y. and Ng, L. T. 2013. γ-Tocotrienol induced cell cycle arrest and apoptosis via activating the Bax-mediated mitochondrial and AMPK signaling pathways in 3T3-L1 adipocytes. Food Chem. Toxicol. 59, 501-513.   DOI
26 Tiainen, M., Vaahtomeri, K., Ylikorkala, A. and Mäkelä, T. P. 2002. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum. Mol. Genet. 11, 1497-1504.   DOI
27 Tomoda, M., Ohara, N., Gonda, R., Shimizu, N., Takada, K., Satoh, Y. and Shirai, S. 1992. An acidic polysaccharide having immunological activities from the rhizome of Cnidium officinale. Chem. Pharm. Bull. (Tokyo) 40, 3025-3029.   DOI
28 Vilches Troya, J. 2005. Understanding cell death: a challenge for biomedicine. An. R. Acad. Nac. Med. (Madr) 122, 631-656.
29 Yi, B., Liu, D., He, M., Li, Q., Liu, T. and Shao, J. 2013. Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells. Oncol. Lett. 6, 583-589.
30 Yinjun, L., Jie, J., Weilai, X. and Xiangming, T. 2004. Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP). Am. J. Hematol. 76, 199-204.   DOI
31 Yoshida, A., Pommier, Y. and Ueda, T. 2006. Endonuclease activation and chromosomal DNA fragmentation during apoptosis in leukemia cells. Int. J. Hematol. 84, 31-37.   DOI
32 Zeqiraj, E., Filippi, B. M., Deak, M., Alessi, D. R. and van Aalten, D. M. 2009. Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science 326, 1707-1711.   DOI