Galla Rhois water extract inhibits lung metastasis by inducing AMPK‑mediated apoptosis and suppressing metastatic properties of colorectal cancer cells

Mun,Jeong‑Geon; Kee,Ji‑Ye; Han,Yo‑Han; Lee,Sullim; Park,Seong‑Hwan; Jeon,Hee   Dong; Hong,Seung‑Heon

doi:10.3892/or.2018.6812

Galla Rhois water extract inhibits lung metastasis by inducing AMPK‑mediated apoptosis and suppressing metastatic properties of colorectal cancer cells

Authors:
- Jeong‑Geon Mun
- Ji‑Ye Kee
- Yo‑Han Han
- Sullim Lee
- Seong‑Hwan Park
- Hee Dong Jeon
- Seung‑Heon Hong
View Affiliations

Affiliations: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang‑Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea, Department of Life Sciences, College of Bio‑Nano Technology, Gachon University, Seongnam 13120, Republic of Korea
Published online on: October 22, 2018 https://doi.org/10.3892/or.2018.6812
Pages: 202-212
Copyright: © Mun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Galla Rhois is a commonly used medicine in East Asia for the treatment of several diseases. However, the effects of Galla Rhois on the metastasis of colorectal cancer (CRC) and the underlying molecular mechanisms have not been studied. We investigated the anti‑metastatic properties of Galla Rhois water extract (GRWE) on metastatic CRC cells. The effect of GRWE on the viability of colon 26 (CT26) cells was evaluated using WST‑8 assay. Annexin V assay and western blot analysis were performed to elucidate the underlying molecular mechanisms involved in apoptosis. GRWE suppressed viability of CT26 cells by inducing apoptosis through the cleavage of caspase‑3 and PARP, downregulation of caspase‑8, caspase‑9, Bcl‑2 and Bcl‑xL, and upregulation of Bax. Metastatic phenotypes such as epithelial‑mesenchymal transition (EMT), migration, and invasion of CRC cells were investigated by real‑time reverse transcription polymerase chain reaction, wound healing assay, and matrigel invasion assay, respectively. Non‑cytotoxic concentrations of GRWE inhibited EMT in CRC cells by regulating the expression of EMT markers. GRWE attenuated cell migration and invasion through the inhibition of matrix metalloproteinase (MMP)‑2 and MMP‑9 activity. Moreover, GRWE suppressed colorectal lung metastasis in vivo, suggestive of its potential application for the treatment of colorectal metastasis.

View Figures

View References

1	Haggar FA and Boushey RP: Colorectal cancer epidemiology: Incidence, mortality survival, and risk factors. Clin Colon Rectal Surg. 22:191–197. 2009. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Dromain C, Caramella C, Dartigues P, Goere D, Ducreux M and Deschamps F: Liver, lung and peritoneal metastases in colorectal cancers: Is the patient still curable? What should the radiologist know. Diagn Interv Imaging. 95:513–523. 2014. View Article : Google Scholar : PubMed/NCBI
4	Tsoulfas G, Pramateftakis MG and Kanellos I: Surgical treatment of hepatic metastases from colorectal cancer. World J Gastrointest Oncol. 3:1–9. 2011. View Article : Google Scholar : PubMed/NCBI
5	Dahabre J, Vasilaki M, Stathopoulos GP, Kondaxis A, Iliadis K, Papadopoulos G, Stathopoulos J, Rigatos S, Vasilikos K and Koutantos J: Surgical management in lung metastases from colorectal cancer. Anticancer Res. 27:4387–4390. 2007.PubMed/NCBI
6	Kim HJ, Kye BH, Lee JI, Lee SC, Lee YS, Lee IK, Kang WK, Cho HM, Moon SW and Oh ST: Surgical resection for lung metastases from colorectal cancer. J Korean Soc Coloproctol. 26:354–358. 2010. View Article : Google Scholar : PubMed/NCBI
7	Martin TA, Ye L, Sanders AJ, Lane J and Jiang WG: Cancer invasion and metastasis: Molecular and cellular perspective. Metastatic Cancer: Clinical and Biological Perspectives. Jandial R: Landes Bioscience; Austin: pp. 135–168. 2013
8	Mishra J, Drummond J, Quazi SH, Karanki SS, Shaw JJ, Chen B and Kumar N: Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol. 86:232–250. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Inv est. 119:1420–1428. 2009. View Article : Google Scholar
10	Garg M: Epithelial-mesenchymal transition-activating transcription factors-multifunctional regulators in cancer. World J Stem Cells. 5:188–195. 2013. View Article : Google Scholar : PubMed/NCBI
11	Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A and Sarkar S: E MT and tumor metastasis. Clin Transl Med. 4:62015. View Article : Google Scholar : PubMed/NCBI
12	Lowe SW and Lin AW: Apoptosis in cancer. Carcinogenesis. 23:485–495. 2000. View Article : Google Scholar
13	Olsson M and Zhivotovsky B: Caspases and cancer. Cell Death Differ. 18:1441–1449. 2011. View Article : Google Scholar : PubMed/NCBI
14	Herceg Z and Wang ZQ: Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res. 477:97–110. 2001. View Article : Google Scholar : PubMed/NCBI
15	Tsujimoto Y: Role of Bcl-2 family proteins in apoptosis: Apoptosomes or mitochondria? Genes Cells. 3:697–707. 1998. View Article : Google Scholar : PubMed/NCBI
16	Wong RS: Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res. 30:872011. View Article : Google Scholar : PubMed/NCBI
17	Monteverde T, Muthalagu N, Port J and Murphy DJ: Evidence of cancer-promoting roles for AMPK and related kinases. FEBS J. 282:4658–4671. 2015. View Article : Google Scholar : PubMed/NCBI
18	Schultze SM, Hemmings BA, Niessen M and Tschopp O: P I3K/AKTMA PK and AMPK signalling: Protein kinases in glucose homeostasis. Expert Rev Mol Med. 14:e12012. View Article : Google Scholar : PubMed/NCBI
19	Hardie DG, Ross FA and Hawley SA: AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 13:251–262. 2012. View Article : Google Scholar : PubMed/NCBI
20	Rehman G, Shehzad A, Khan AL and Hamayun M: Role of AMP-activated protein kinase in cancer therapy. Arch Pharm. 347:457–468. 2014. View Article : Google Scholar
21	Baba Y, Nosho K, Shima K, Meyerhardt JA, Chan AT, Engelman JA, Cantley LC, Loda M, Giovannucci E, Fuchs CS and Ogino S: Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer. Br J Cancer. 103:1025–1033. 2010. View Article : Google Scholar : PubMed/NCBI
22	Ahn YJ, Lee CO, Kweon JH, Ahn JW and Park JH: Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria. J Appl Microbiol. 84:439–443. 1998. View Article : Google Scholar : PubMed/NCBI
23	Go J, Kim JE, Koh EK, Song SH, Seong JE, Park CK, Lee HA, Kim HS, Lee JH, An BS, et al: Hepatotoxicity and nephrotoxicity of gallotannin-enriched extract isolated from Galla Rhois in ICR mice. Lab Anim Res. 31:101–110. 2015. View Article : Google Scholar : PubMed/NCBI
24	Kim SH, Park HH, Lee S, Jun CD, Choi BJ, Kim SY, Kim SH, Kim DK, Park JS, Chae BS, et al: The anti-anaphylactic effect of the gall of Rhus javanica is mediated through inhibition of histamine release and inflammatory cytokine secretion. Int Immunopharmacol. 5:1820–1829. 2005. View Article : Google Scholar : PubMed/NCBI
25	Yim NH, Gu MJ, Hwang YH, Cho WK and Ma JY: Water extract of Galla Rhois with steaming process enhances apoptotic cell death in human colon cancer cells. Integr Med Res. 5:284–292. 2016. View Article : Google Scholar : PubMed/NCBI
26	Lee HJ, Seo NJ, Jeong SJ, Park Y, Jung DB, Koh W, Lee HJ, Lee EO, Ahn KS, Ahn KS, et al: Oral administration of penta-O-galloyl-β-D-glucose suppresses triple-negative breast cancer xenograft growth and metastasis in strong association with JAK1-STAT3 inhibition. Carcinogenesis. 32:804–811. 2011. View Article : Google Scholar : PubMed/NCBI
27	Deiab S, Mazzio E, Eyunni S, McTier O, Mateeva N, Elshami F and Soliman KF: 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis inhibits human LDH-A and attenuates cell proliferation in MDA-MB-231 breast cancer cells. Evid Based Complement Alternat Med. 2015:2769462015. View Article : Google Scholar : PubMed/NCBI
28	Ata N, Oku T, Hattori M, Fujii H, Nakajima M and Saiki I: Inhibition by galloylglucose (GG6-10) of tumor invasion through extracellular matrix and gelatinase-mediated degradation of type IV collagens by metastatic tumor cells. Oncol Res. 8:503–511. 1996.PubMed/NCBI
29	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
30	Chen MB, Zhang Y, Wei MX, Shen W, Wu XY, Yao C and Lu PH: Activation of AMP-activated protein kinase (AMPK) mediates plumbagin-induced apoptosis and growth inhibition in cultured human colon cancer cells. Cell Signal. 25:1993–2002. 2013. View Article : Google Scholar : PubMed/NCBI
31	Chai Y, Lee HJ, Shaik AA, Nkhata K, Xing C, Zhang J, Jeong SJ, Kim SH and Lu J: Penta-O-galloyl-beta-D-glucose induces G₁ arrest and DNA replicative S-phase arrest independently of cyclin-dependent kinase inhibitor 1A, cyclin-dependent kinase inhibitor 1B and P53 in human breast cancer cells and is orally active against triple negative xenograft growth. Breast Cancer Res. 12:R672010. View Article : Google Scholar : PubMed/NCBI
32	Li W, Saud SM, Young MR, Chen G and Hua B: Targeting AMPK for cancer prevention and treatment. Oncotarget. 6:7365–7378. 2015.PubMed/NCBI
33	Plews RL, Mohd Yusof A, Wang C, Saji M, Zhang X, Chen CS, Ringel MD and Phay JE: A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth. J Clin Endocrinol Metab. 100:E748–E756. 2015. View Article : Google Scholar : PubMed/NCBI
34	Kim MJ, Yun H, Kim DH, Kang I, Choe W, Kim SS and Ha J: AMP-activated protein kinase determines apoptotic sensitivity of cancer cells to ginsenoside-Rh2. J Ginseng Res. 38:16–21. 2014. View Article : Google Scholar : PubMed/NCBI
35	Son H and Moon A: Epithelial-mesenchymal transition and cell invasion. Toxicol Res. 26:245–252. 2010. View Article : Google Scholar : PubMed/NCBI
36	Plati J, Bucur O and Khosravi-Far R: Apoptotic cell signaling in cancer progression and therapy. Integr Biol. 3:279–296. 2011. View Article : Google Scholar
37	Takeda K, Stagg J, Yagita H, Okumura K and Smyth MJ: Targeting death-inducing receptors in cancer therapy. Oncogene. 26:3745–3757. 2007. View Article : Google Scholar : PubMed/NCBI
38	Su Z, Yang Z, Xu Y, Chen Y and Yu Q: Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 14:482015. View Article : Google Scholar : PubMed/NCBI
39	Hideshima T and Anderson KC: Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer. 2:927–937. 2002. View Article : Google Scholar : PubMed/NCBI
40	Han YH, Kee JY, Kim DS, Mun JG, Jeong MY, Park SH, Choi BM, Park SJ, Kim HJ, Um JY, et al: Arctigenin inhibits lung metastasis of colorectal cancer by regulating cell viability and metastatic phenotypes. Molecules. 21:E11352016. View Article : Google Scholar : PubMed/NCBI
41	Huang T, Xiao Y, Yi L, Li L, Wang M, Tian C, Ma H, He K, Wang Y, Han B, et al: Coptisine from rhizoma coptidis suppresses hct-116 cells-related tumor growth in vitro and in vivo. Sci Rep. 7:385242017. View Article : Google Scholar : PubMed/NCBI
42	Lu Z and Xu S: ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 58:621–631. 2006. View Article : Google Scholar : PubMed/NCBI
43	Grossi V, Peserico A, Tezil T and Simone C: p38α MAPK pathway: A key factor in colorectal cancer therapy and chemoresistance. World J Gastroenterol. 20:9744–9758. 2014. View Article : Google Scholar : PubMed/NCBI
44	Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C and Pan H: p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett. 344:174–179. 2014. View Article : Google Scholar : PubMed/NCBI
45	Chen L, Mayer JA, Krisko TI, Speers CW, Wang T, Hilsenbeck SG and Brown PH: Inhibition of the p38 kinase suppresses the proliferation of human ER-negative breast cancer cells. Cancer Res. 69:8853–8861. 2009. View Article : Google Scholar : PubMed/NCBI
46	Thornton TM and Rincon M: Non-classical p38 map kinase functions: Cell cycle checkpoints and survival. Int J Biol Sci. 5:44–51. 2009. View Article : Google Scholar : PubMed/NCBI
47	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
48	Lindsey S and Langhans SA: Crosstalk of oncogenic signaling pathways during epithelial-mesenchymal transition. Front Oncol. 4:3582014. View Article : Google Scholar : PubMed/NCBI
49	Derycke LD and Bracke ME: N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Biol. 48:463–476. 2004. View Article : Google Scholar : PubMed/NCBI
50	Gialeli C, Theocharis AD and Karamanos NK: Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 278:16–27. 2011. View Article : Google Scholar : PubMed/NCBI
51	Urueña C, Mancipe J, Hernandez J, Castañeda D, Pombo L, Gomez A, Asea A and Fiorentino S: Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model. BMC Complement. Altern Med. 13:742013.
52	Zhao T, Sun Q, del Rincon SV, Lovato A, Marques M and Witcher M: Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo. PLoS One. 9:e928532014. View Article : Google Scholar : PubMed/NCBI
53	Al-Halabi R, Bou Chedid M, Abou Merhi R, El-Hajj H, Zahr H, Schneider-Stock R, Bazarbachi A and Gali-Muhtasib H: Gallotannin inhibits NFκB signaling and growth of human colon cancer xenografts. Cancer Biol Ther. 12:59–68. 2011. View Article : Google Scholar : PubMed/NCBI