Sorbus commixta water extract induces apoptotic cell death via a ROS‑dependent pathway

Moon,Seong‑Cheol; Choi,Hee‑Jung; Chung,Tae‑Wook; Lee,Jung‑Hee; Lee,Syng‑Ook; Jung,Myeong Ho; Kim,Byung Joo; Choi,Jun‑Yong; Ha,Ki‑Tae

doi:10.3892/ol.2018.9217

Sorbus commixta water extract induces apoptotic cell death via a ROS‑dependent pathway

Authors:
- Seong‑Cheol Moon
- Hee‑Jung Choi
- Tae‑Wook Chung
- Jung‑Hee Lee
- Syng‑Ook Lee
- Myeong Ho Jung
- Byung Joo Kim
- Jun‑Yong Choi
- Ki‑Tae Ha
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Affiliations: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea, Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea, Department of Food Science and Technology, Keimyung University, Daegu 42601, Republic of Korea
Published online on: July 25, 2018 https://doi.org/10.3892/ol.2018.9217
Pages: 4193-4200
Copyright: © Moon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The stembark of Sorbus commixta Hedl. has been used for treating asthma, bronchitis, gastritis and edema. However, the anticancer and proapoptotic effects of the water extract of the stembark of S. commixta (SCE) remain unknown. In the present study, it was shown that SCE inhibited the cell viability of the hepatocellular carcinoma cell lines Hep3B and HepG2, and of the colon carcinoma cell line HCT116. DNA content analysis indicated that SCE increased the sub‑G1 population of HCT116 cells. In addition, degradation of nuclear DNA and levels of proapoptotic cascade components, including caspase‑9, caspase‑3 and poly ADP‑ribose polymerase, were augmented by SCE treatment. Mitochondrial membrane potential and the ratio of B‑cell lymphoma‑2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) were also reduced. Furthermore, SCE increased the expression of proapoptotic proteins, including p21, p27 and p53. Mouse double minute 2 homology, a negative regulator of p53, was cleaved by SCE treatment. Intracellular reactive oxygen species (ROS) production was also increased by SCE treatment. However, the SCE‑induced cytotoxic effects and the increased expression of proapoptotic proteins, including p53 and p21, and reduced Bcl‑2/Bax ratio, could be attenuated by N‑acetyl cysteine, an ROS inhibitor. Taken together, these results indicate that SCE is a potent proapoptotic herbal medicine, which exerts its effects via the ROS‑mediated mitochondrial pathway.

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1	Baig S, Seevasant I, Mohamad J, Mukheem A, Huri HZ and Kamarul T: Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Cell Death Dis. 7:e20582016. View Article : Google Scholar : PubMed/NCBI
2	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
3	Fulda S and Debatin KM: Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 25:4798–4811. 2006. View Article : Google Scholar : PubMed/NCBI
4	Pistritto G, Trisciuoglio D, Ceci C, Garufi A and D'Orazi G: Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 8:603–619. 2016. View Article : Google Scholar : PubMed/NCBI
5	Wang H, Yin Y, Wang P, Xiong C, Huang L, Li S, Li X and Fu L: Current situation and future usage of anticancer drug databases. Apoptosis. 21:778–794. 2016. View Article : Google Scholar : PubMed/NCBI
6	Gill BS, Kumar S and Navgeet: Triterpenes in cancer: Significance and their influence. Mol Biol Rep. 43:881–896. 2016. View Article : Google Scholar : PubMed/NCBI
7	Milani A, Basirnejad M, Shahbazi S and Bolhassani A: Carotenoids: Biochemistry, pharmacology and treatment. Br J Pharmacol. 174:1290–1324. 2017. View Article : Google Scholar : PubMed/NCBI
8	Niedzwiecki A, Roomi MW, Kalinovsky T and Rath M: Anticancer efficacy of polyphenols and their combinations. Nutrients. 8:E5522016. View Article : Google Scholar : PubMed/NCBI
9	Zhang YS, Shen Q and Li J: Traditional Chinese medicine targeting apoptotic mechanisms for esophageal cancer therapy. Acta Pharmacol Sin. 37:295–302. 2016. View Article : Google Scholar : PubMed/NCBI
10	McAllister H: The genus sorbus: Mountain ash and other rowansRoyal Botanic Gardens. KEW; Surrey, UK: 2005
11	Yang G and An HJ: β-sitosteryl-3-O-β-glucopyranoside isolated from the bark of Sorbus commixta ameliorates pro-inflammatory mediators in RAW 264.7 macrophages. Immunopharmacol Immunotoxicol. 36:70–77. 2014. View Article : Google Scholar : PubMed/NCBI
12	Yu T, Lee YJ, Jang HJ, Kim AR, Hong S, Kim TW, Kim MY, Lee J, Lee YG and Cho JY: Anti-inflammatory activity of Sorbus commixta water extract and its molecular inhibitory mechanism. J Ethnopharmacol. 134:493–500. 2011. View Article : Google Scholar : PubMed/NCBI
13	Kang DG, Sohn EJ, Lee AS, Kim JS, Lee DH and Lee HS: Methanol extract of Sorbus commixta cortex prevents vascular inflammation in rats with a high fructose-induced metabolic syndrome. Am J Chin Med. 35:265–277. 2007. View Article : Google Scholar : PubMed/NCBI
14	Sohn EJ, Kang DG, Choi DH, Lee AS, Mun YJ, Woo WH, Kim JS and Lee HS: Effect of methanol extract of Sorbus cortex in a rat model of L-NAME-induced atherosclerosis. Biol Pharm Bull. 28:1239–1243. 2005. View Article : Google Scholar : PubMed/NCBI
15	Sohn EJ, Kang DG, Mun YJ, Woo WH and Lee HS: Anti-atherogenic effects of the methanol extract of Sorbus cortex in atherogenic-diet rats. Biol Pharm Bull. 28:1444–1449. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lee SO, Lee HW, Lee IS and Im HG: The pharmacological potential of Sorbus commixta cortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated rats. J Pharm Pharmacol. 58:685–693. 2006. View Article : Google Scholar : PubMed/NCBI
17	Liu QF, Lee JH, Kim YM, Lee S, Hong YK, Hwang S, Oh Y, Lee K, Yun HS, Lee IS, et al: In vivo screening of traditional medicinal plants for neuroprotective activity against Aβ42 cytotoxicity by using drosophila models of Alzheimer's disease. Biol Pharm Bull. 38:1891–1901. 2015. View Article : Google Scholar : PubMed/NCBI
18	Bae JT, Sim GS, Kim JH, Pyo HB, Yun JW and Lee BC: Antioxidative activity of the hydrolytic enzyme treated Sorbus commixta Hedl. and its inhibitory effect on matrix metalloproteinase-1 in UV irradiated human dermal fibroblasts. Arch Pharm Res. 30:1116–1123. 2007. View Article : Google Scholar : PubMed/NCBI
19	Na M, Kim BY, Osada H and Ahn JS: Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta. J Enzyme Inhib Med Chem. 24:1056–1059. 2009. View Article : Google Scholar : PubMed/NCBI
20	Nikolaienko RM, Agyekum B and Bouyain S: Receptor protein tyrosine phosphatases and cancer: New insights from structural biology. Cell Adh Migr. 6:356–364. 2012. View Article : Google Scholar : PubMed/NCBI
21	Ostman A, Hellberg C and Böhmer FD: Protein-tyrosine phosphatases and cancer. Nat Rev Cancer. 6:307–320. 2006. View Article : Google Scholar : PubMed/NCBI
22	Millimouno FM, Dong J, Yang L, Li J and Li X: Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prev Res (Phila). 7:1081–1107. 2014. View Article : Google Scholar : PubMed/NCBI
23	Safarzadeh E, Shotorbani Sandoghchian S and Baradaran B: Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 4:421–427. 2014.PubMed/NCBI
24	Brunelle JK and Letai A: Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 122:437–441. 2009. View Article : Google Scholar : PubMed/NCBI
25	Kitagishi Y, Kobayashi M and Matsuda S: Protection against cancer with medicinal herbs via activation of tumor suppressor. J Oncol. 2012:2365302012. View Article : Google Scholar : PubMed/NCBI
26	Gao J, Morgan WA, Sanchez-Medina A and Corcoran O: The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells. Toxicol Appl Pharmacol. 254:221–228. 2011. View Article : Google Scholar : PubMed/NCBI
27	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
28	Li B, Zhao J, Wang CZ, Searle J, He TC, Yuan CS and Du W: Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett. 301:185–192. 2011. View Article : Google Scholar : PubMed/NCBI
29	Hastak K, Agarwal MK, Mukhtar H and Agarwal ML: Ablation of either p21 or Bax prevents p53-dependent apoptosis induced by green tea polyphenol epigallocatechin-3-gallate. FASEB J. 19:789–791. 2005. View Article : Google Scholar : PubMed/NCBI
30	Masuda M, Suzui M and Weinstein IB: Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res. 7:4220–4229. 2001.PubMed/NCBI
31	Abbas T and Dutta A: p21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer. 9:400–414. 2009. View Article : Google Scholar : PubMed/NCBI
32	Levkau B, Koyama H, Raines EW, Clurman BE, Herren B, Orth K, Roberts JM and Ross R: Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: Role of a caspase cascade. Mol Cell. 1:553–563. 1998. View Article : Google Scholar : PubMed/NCBI
33	Chipuk JE and Green DR: Cytoplasmic p53: Bax and forward. Cell Cycle. 3:429–431. 2004. View Article : Google Scholar : PubMed/NCBI
34	Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B and Reed JC: Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 9:1799–1805. 1994.PubMed/NCBI
35	Oren M: Regulation of the p53 tumor suppressor protein. J Biol Chem. 274:36031–36034. 1999. View Article : Google Scholar : PubMed/NCBI
36	Kruse JP and Gu W: Modes of p53 regulation. Cell. 137:609–622. 2009. View Article : Google Scholar : PubMed/NCBI
37	Ryan KM, Phillips AC and Vousden KH: Regulation and function of the p53 tumor suppressor protein. Curr Opin Cell Biol. 13:332–337. 2001. View Article : Google Scholar : PubMed/NCBI
38	Oliver TG, Meylan E, Chang GP, Xue W, Burke JR, Humpton TJ, Hubbard D, Bhutkar A and Jacks T: Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop. Mol Cell. 43:57–71. 2011. View Article : Google Scholar : PubMed/NCBI
39	Pochampally R, Fodera B, Chen L, Shao W, Levine EA and Chen J: A 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells. Oncogene. 17:2629–2636. 1998. View Article : Google Scholar : PubMed/NCBI
40	Macip S, Igarashi M, Berggren P, Yu J, Lee SW and Aaronson SA: Influence of induced reactive oxygen species in p53-mediated cell fate decisions. Mol Cell Biol. 23:8576–8585. 2003. View Article : Google Scholar : PubMed/NCBI
41	Johnson TM, Yu ZX, Ferrans VJ, Lowenstein RA and Finkel T: Reactive oxygen species are downstream mediators of p53-dependent apoptosis. Proc Natl Acad Sci USA. 93:11848–11852. 1996. View Article : Google Scholar : PubMed/NCBI
42	Liu B, Chen Y and St Clair DK: ROS and p53: A versatile partnership. Free Radic Biol Med. 44:1529–1535. 2008. View Article : Google Scholar : PubMed/NCBI
43	Polyak K, Xia Y, Zweier JL, Kinzler KW and Vogelstein B: A model for p53-induced apoptosis. Nature. 389:300–305. 1997. View Article : Google Scholar : PubMed/NCBI
44	Choi D, Hwang S, Lee E, Yoon S, Yoon BK and Bae D: Expression of mitochondria-dependent apoptosis genes (p53, Bax, and Bcl-2) in rat granulosa cells during follicular development. J Soc Gynecol Investig. 11:311–317. 2004. View Article : Google Scholar : PubMed/NCBI
45	Yang Y, Karakhanova S, Hartwig W, D'Haese JG, Philippov PP, Werner J and Bazhin AV: Mitochondria and mitochondrial ROS in cancer: Novel targets for anticancer therapy. J Cell Physiol. 231:2570–2581. 2016. View Article : Google Scholar : PubMed/NCBI
46	Raudone L, Raudonis R, Gaivelytė K, Pukalskas A, Viškelis P, Venskutonis PR and Janulis V: Phytochemical and antioxidant profiles of leaves from different Sorbus L. species. Nat Prod Res. 29:281–285. 2015. View Article : Google Scholar : PubMed/NCBI
47	Bhatt LR, Bae MS, Kim BM, Oh GS and Chai KY: A chalcone glycoside from the fruits of Sorbus commixta Hedl. Molecules. 14:5323–5327. 2009. View Article : Google Scholar : PubMed/NCBI
48	Liu Y, Bi T, Dai W, Wang G, Qian L, Shen G and Gao Q: Lupeol induces apoptosis and cell cycle arrest of human osteosarcoma cells through PI3K/AKT/mTOR pathway. Technol Cancer Res Treat. 15:NP16–NP24. 2016. View Article : Google Scholar : PubMed/NCBI
49	Sook SH, Lee HJ, Kim JH, Sohn EJ, Jung JH, Kim B, Kim JH, Jeong SJ and Kim SH: Reactive oxygen species-mediated activation of AMP-activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta-sitosterol-induced apoptosis in multiple myeloma U266 cells. Phytother Res. 28:387–394. 2014. View Article : Google Scholar : PubMed/NCBI