Rhus verniciflua Stokes extract induces inhibition of cell growth and apoptosis in human chronic myelogenous leukemia K562 cells

Lee,Kyung-Wook; Um,Eun-Sik; Jung,Bo-Bae; Choi,Eun-Sol; Kim,Eun-Young; Lee,Seungbo; Jang,Eungyeong; Lee,Jang-Hoon; Kim,Youngchul

doi:10.3892/or.2018.6179

Rhus verniciflua Stokes extract induces inhibition of cell growth and apoptosis in human chronic myelogenous leukemia K562 cells

Authors:
- Kyung-Wook Lee
- Eun-Sik Um
- Bo-Bae Jung
- Eun-Sol Choi
- Eun-Young Kim
- Seungbo Lee
- Eungyeong Jang
- Jang-Hoon Lee
- Youngchul Kim
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Affiliations: Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
Published online on: January 3, 2018 https://doi.org/10.3892/or.2018.6179
Pages: 1141-1147

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Abstract

Rhus verniciflua Stokes has been widely used as a traditional medicinal plant with a variety of pharmacological activities. We investigated the mechanisms involved in mediating the effects of Rhus verniciflua Strokes (R. verniciflua) extract in human chronic myelogenous leukemia K562 cells, including caspase-dependent apoptotic pathways related to cell-cycle arrest, as well as the inhibition of nuclear factor NF-κB activation and upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway. R. verniciflua extract suppressed the abnormal cellular proliferation of K562 cells in a dose- and time‑dependent manner and increased the quantitative proportions of cells involved in the early and late process of apoptosis. Furthermore, R. verniciflua extract significantly mediated the mRNA levels of pro-apoptotic and anti-apoptotic regulators, such as Bcl-2, Bax, Mcl-1 and survivin in apoptotic cells. Particularly, the treatment of K562 cells with R. verniciflua extract augmented the caspase‑3 activity and increased the expression of caspase‑3 protein, while co-treatment with R. verniciflua extract and the permeant pan‑caspase inhibitor Z-VAD-FMK and caspase‑3 inhibitor Z-DEVD-FMK inversely enhanced the proliferation of K562 cells. The extract of R. verniciflua inhibited the activation of NF-κB and the phosphorylation of ERK. Collectively, these results indicated that the extract of R. verniciflua inhibited the proliferation of human chronic myelogenous leukemia K562 cells by activating the apoptotic process via caspase‑3 overexpression and the regulation of the NF-κB and MAPK signaling.

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1	Choi W, Jung H, Kim K and Lee S, Yoon S, Park J, Kim S, Cheon S, Eo W and Lee S: Rhus verniciflua stokes against advanced cancer: A perspective from the Korean Integrative Cancer Center. J Biomed Biotechnol. 2012:8742762012. View Article : Google Scholar : PubMed/NCBI
2	Lim KT, Hu C and Kitts DD: Antioxidant activity of a Rhus verniciflua Stokes ethanol extract. Food Chem Toxicol. 39:229–237. 2001. View Article : Google Scholar : PubMed/NCBI
3	Kitts DD and Lim KT: Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS). J Toxicol Environ Health A. 64:357–371. 2001. View Article : Google Scholar : PubMed/NCBI
4	Lee JD, Huh JE, Jeon G, Yang HR, Woo HS, Choi DY and Park DS: Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models. Int Immunopharmacol. 9:268–276. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lee JC, Lim KT and Jang YS: Identification of Rhus verniciflua Stokes compounds that exhibit free radical scavenging and anti-apoptotic properties. Biochim Biophys Acta. 1570:181–191. 2002. View Article : Google Scholar : PubMed/NCBI
6	Lee JC, Lee KY, Kim J, Na CS, Jung NC, Chung GH and Jang YS: Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells. Food Chem Toxicol. 42:1383–1388. 2004. View Article : Google Scholar : PubMed/NCBI
7	Jang HS, Kook SH, Son YO, Kim JG, Jeon YM, Jang YS, Choi KC, Kim J, Han SK, Lee KY, et al: Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochim Biophys Acta. 1726:309–316. 2005. View Article : Google Scholar : PubMed/NCBI
8	Lee JC, Kim J and Jang YS: Ethanol-eluted extract of Rhus verniciflua stokes inhibits cell growth and induces apoptosis in human lymphoma cells. J Biochem Mol Biol. 36:337–343. 2003.PubMed/NCBI
9	Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
10	Wyllie AH, Kerr JF and Currie AR: Cell death: The significance of apoptosis. Int Rev Cytol. 68:251–306. 1980. View Article : Google Scholar : PubMed/NCBI
11	Levine B, Sinha S and Kroemer G: Bcl-2 family members: Dual regulators of apoptosis and autophagy. Autophagy. 4:600–606. 2008. View Article : Google Scholar :
12	Stanciu M, Wang Y, Kentor R, Burke N, Watkins S, Kress G, Reynolds I, Klann E, Angiolieri MR, Johnson JW, et al: Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J Biol Chem. 275:12200–12206. 2000. View Article : Google Scholar : PubMed/NCBI
13	Aggarwal BB: Nuclear factor-kappaB: The enemy within. Cancer Cell. 6:203–208. 2004. View Article : Google Scholar : PubMed/NCBI
14	Yun-Yang W, Yu-Min D, Fang-Xing Y, Ying X, Rong-Zhi C and Kennedy JF: Purification and characterization of hydrosoluble components from the sap of Chinese lacquer tree Rhus vernicifera. Int J Biol Macromol. 38:232–240. 2006. View Article : Google Scholar : PubMed/NCBI
15	Lee SH, Choi WC and Yoon SW: Impact of standardized Rhus verniciflua stokes extract as complementary therapy on metastatic colorectal cancer: A Korean single-center experience. Integr Cancer Ther. 8:148–152. 2009. View Article : Google Scholar : PubMed/NCBI
16	Choi HS, Seo HS, Kim SR, Choi YK, Jang BH, Shin YC and Ko SG: Anti-inflammatory and anti-proliferative effects of Rhus verniciflua Stokes in RAW264.7 cells. Mol Med Rep. 9:311–315. 2014. View Article : Google Scholar : PubMed/NCBI
17	Park SW and Kim YI: Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs. Int J Oncol. 43:1169–1175. 2013. View Article : Google Scholar : PubMed/NCBI
18	Li J and Yuan J: Caspases in apoptosis and beyond. Oncogene. 27:6194–6206. 2008. View Article : Google Scholar : PubMed/NCBI
19	Yin Y, Chen W, Tang C, Ding H, Jang J, Weng M, Cai Y and Zou G: NF-κB, JNK and p53 pathways are involved in tubeimoside-1-induced apoptosis in HepG2 cells with oxidative stress and G₂/M cell cycle arrest. Food Chem Toxicol. 49:3046–3054. 2011. View Article : Google Scholar : PubMed/NCBI
20	Burlacu A: Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med. 7:249–257. 2003. View Article : Google Scholar : PubMed/NCBI
21	Kuwana T and Newmeyer DD: Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol. 15:691–699. 2003. View Article : Google Scholar : PubMed/NCBI
22	Reed JC: Apoptosis-targeted therapies for cancer. Cancer Cell. 3:17–22. 2003. View Article : Google Scholar : PubMed/NCBI
23	Zhu W, Hu H, Qiu P and Yan G: Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism. Oncol Rep. 22:1397–1401. 2009.PubMed/NCBI
24	Rubinfeld H and Seger R: The ERK cascade: A prototype of MAPK signaling. Mol Biotechnol. 31:151–174. 2005. View Article : Google Scholar : PubMed/NCBI
25	Cui Q, Tashiro S, Onodera S, Minami M and Ikejima T: Autophagy preceded apoptosis in oridonin-treated human breast cancer MCF-7 cells. Biol Pharm Bull. 30:859–864. 2007. View Article : Google Scholar : PubMed/NCBI
26	Lee SJ, Park K, Ha SD, Kim WJ and Moon SK: Gleditsia sinensis thorn extract inhibits human colon cancer cells: The role of ERK1/2, G2/M-phase cell cycle arrest and p53 expression. Phytother Res. 24:1870–1876. 2010. View Article : Google Scholar : PubMed/NCBI
27	Yim NH, Kim A, Liang C, Cho WK and Ma JY: Guibitang, a traditional herbal medicine, induces apoptotic death in A431 cells by regulating the activities of mitogen-activated protein kinases. BMC Complement Altern Med. 14:3442014. View Article : Google Scholar : PubMed/NCBI
28	Du J, Chen C, Sun Y, Zheng L and Wang W: Ponicidin suppresses HT29 cell growth via the induction of G1 cell cycle arrest and apoptosis. Mol Med Rep. 12:5816–5820. 2015. View Article : Google Scholar : PubMed/NCBI