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Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 2,  2016, pp.119-128
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2232
 Title & Authors
Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway
Rahman, Md. Ataur; Bishayee, Kausik; Huh, Sung-Oh;
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Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK- activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy.
Angelica polymorpha;apoptosis;Bax/Bcl-2 ratio;caspase;neuroblastoma;
 Cited by
Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway, World Journal of Gastroenterology, 2017, 23, 6, 1010  crossref(new windwow)
Besbes, S., Massoud, M., Marc, Pocard., and Christian, B. (2015). New dimension in therapeutic targeting of BCL-2 family proteins. Oncotarget 6, 12862-12871. crossref(new window)

Bodur, C., and Basaga, H. (2012). Bcl-2 inhibitors: emerging drugs in cancer therapy. Curr Med Chem. 19, 1804-1820. crossref(new window)

Brodeur, G.M. (2003). Neuroblastoma: biological insights into a clinical enigma. Nat. Rev. Cancer 3, 203-216. crossref(new window)

Castel, V., Grau, E., Noguera, R., and Martinez, F. (2007). Molecular biology of neuroblastoma. Clin. Transl. Oncol. 9, 478- 483. crossref(new window)

Estaquier, J., Francois, V., Jean-Luc V., and Bernard, M. (2012). The mitochondrial pathways of apoptosis. Adv. Exp. Med. Biol. 942,157-83. crossref(new window)

Fiandalo, M.V., and Kyprianou, N. (2012). Caspase control: protagonists of cancer cell apoptosis. Exp. Oncol. 34, 165-175

Flaherty, K.T., Infante, J.R., Daud, A., Gonzalez, R., Kefford, R.F., Sosman, J., Hamid, O., Schuchter, L., Cebon, J., Ibrahim, N., et al. (2012). Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl. J. Med. 367, 1694-1703. crossref(new window)

Hector, S., and Jochen, H.M P. (2009). Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review. Biochim. Biophys. Acta 1795, 117-129.

Hoye, A.T., Jennifer, E.D., Peter, W., Mitchell, P.F., and Valerian, E.K. (2008). Targeting mitochondria. Acc. Chem. Res. 41, 87-97. crossref(new window)

Kwon, Y.H., Bishayee, K., Rahman, A., Hong, J.S., Lim, S.S., and Huh, S.O. (2015). Morus alba accumulates reactive oxygen species to initiate apoptosis via FOXO-caspase 3-dependent pathway in neuroblastoma cells. Mol. Cells 38, 630-637. crossref(new window)

Kroemer, G. (1997). The proto-oncogene Bcl-2 and Its role in regulating apoptosis. Nat. Med. 3, 614-620. crossref(new window)

Maris, J.M., Michael, D.H., Rochelle, B., and Susan, L.C. (2007). Neuroblastoma. Lancet 369, 2106-2120. crossref(new window)

Maris, J.M., Mosse, Y.P., Bradfield, J.P., Hou, C., Monni, S., Scott, R.H., Asgharzadeh, S., Attiyeh, E.F., Diskin, S.J., Laudenslager, M., et al. (2008). Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl. J. Med. 358, 2585- 2593. crossref(new window)

Nascimento, Pde S., Ornellas, A. A., Campos M. M., Scheiner, M.A., Fiedler, W., and Alves, G. (2004). Bax and bcl-2 imbalance and HPB infection in penile tumors and adjacent tissues. Prog Urol. 14, 353-359.

Pinto, N.R., Applebaum M.A., Volchenboum, S.L., Matthay, K.K., London, W.B., Ambros, P.F., Nakagawara , A., Berthold, F., Schleiermacher, G., Park, J.R., et al. (2015). Advances in risk classification and treatment strategies for neuroblastoma. J. Clin. Oncol. 20, 3008-3017.

Rahman, Md A., Nam-Ho, Kim., and Sung-Oh, Huh. (2013). Cytotoxic effect of gambogic acid on SH-SY5Y neuroblastoma cells is mediated by intrinsic caspase-dependent signaling pathway. Mol. Cell Biochem. 377, 187-196. crossref(new window)

Reed, J.C. (1997). Double identity for proteins of the Bcl-2 family. Nature 387, 773-776. crossref(new window)

Roy, S., and Nicholson D. W. (2000). Cross-talk in cell death signaling. J. Exp. Med. 192, 21-26. crossref(new window)

Schrey, D., Vaidya, S.J., Levine, D., Pearson, A.D., and Moreno, L. (2015). Additional therapies to improve metastatic response to induction therapy in children with high-risk neuroblastoma. J. Pediatr. Hematol. Oncol. 37, e150-e153. crossref(new window)

Shah, S.Z., Zhao, D., Khan, S.H., and Yang, L. (2015). Unfolded protein response pathways in neurodegenerative diseases. J. Mol. Neurosci. doi:10.1007/s12031-015-0633-3. crossref(new window)

Shi, X., Chen, X., Li, X., Lan, X., Zhao, C., Liu, S., Huang, H., Liu, N., Liao, S., Song, W., et al. (2014). Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation. Clin. Cancer Res. 20, 151-163. crossref(new window)

Sonawane, P., Cho, H.E., Tagde, A., Verlekar, D., Yu, A.L., Reynolds, C.P., and Kang, M.H. (2014). Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and antitumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13- cis-retinoic acid in neuroblastoma. Br. J. Pharmacol. 171, 5330- 5344. crossref(new window)

Takahashi-Yanaga, F., and Sasaguri, T. (2009). Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)- mediated signal transduction pathway: inhibitors of the Wnt/beta-catenin signaling pathway as novel anticancer drugs. J. Pharmacol. Sci. 109, 179-183. crossref(new window)

Wang, J., Zhu, L., Zou, K., Cheng, F., Dan, F., Guo, Z., Cai, Z., and Yang, J. (2009). The anti-ulcer activities of bisabolangelone from Angelica polymorpha. J. Ethnopharmacol. 123, 343-346. crossref(new window)

Yang, Y., Zhang, Y., Ren, F.X., Yu, N.J., Xu, R., and Zhao, Y.M. (2013). Chemical constituents from the roots of Angelica polymorpha Maxim. Yao Xue Xue Bao 48, 718-722.

Yee, K.S., Wilkinson, S., James, J., Ryan, K.M., and Vousden, K.H. (2009). PUMA- and bax-induced autophagy contributes to apoptosis. Cell Death Differ. 16, 1135-1145. crossref(new window)

Zhang, C.L., Wu, L.J., Tashiro, S., Onodera, S., and Ikejima, T. (2004). Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway. Acta Pharmacol. Sin. 25, 691-698.