AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (2.6 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Malvidin-3-galactoside from blueberry suppresses the growth and metastasis potential of hepatocellular carcinoma cell Huh-7 by regulating apoptosis and metastases pathways

Jie LinaJinlong Tiana,bChi Shua,bZhen ChengaYunen LiucWeisheng WangdRuihai LiueBin Lia,b,c( )Yuehua Wanga,b,c( )
National R & D Professional Center For Berry Processing, Shenyang Agricultural University, Liaoning, PR China
Key Laborotary of Healthy Food Nutrition and Innovative Manufacturing, Liaoning, PR China
Emergency Medicine Department of General Hospital of Shenyang Military Command, Laboratory of Rescue Center of Severe Trauma PLA, Liaoning, PR China
Shenyang Blueberry Industry co. LTD., Liaoning, PR China
Department of Food Science, Cornell University, Ithaca, NY, USA

Peer review under responsibility of KeAi Communications Co., Ltd.

Show Author Information

Abstract

Malvidin-3-galactoside (Mv-3-gal) is the major anthocyanin monomer in blueberry anthocyanins. The compound is well-characterized by its anti-oncogenesis function in multiple organs including liver. In the current study, the mechanism driving the anti-hepatocellular carcinoma (HCC) function of Mv-3-gal was further explored by focusing on apoptosis and metastases pathways. HCC cell line Huh-7 was firstly administrated with Mv-3-gal of different concentrations and the effect of Mv-3-gal on cell proliferation, apoptosis, colony formation ability, metastasis potential as well as the activity of Akt/PTEN and MAPK pathways was assessed. The results showed that Mv-3-gal inhibited the cell proliferation and colony formation ability, induced cell cycle arrest and apoptosis in a dose-dependent manner. Regarding the metastasis potential, Mv-3-gal suppressed the migration and invasion potential of Huh-7 cells by regulating MMPs expression. Taken together, the findings highlighted the anti-HCC potent of Mv-3-gal, which was associated with the inhibition of Akt/PTEN, MAPK and MMP pathways.

References

[1]

S. Norberto, S. Silva, M. Meireles, et al., Blueberry anthocyanins in health promotion: a metabolic overview, J. Funct. Foods 5 (2013) 1518–1528, http://dx.doi.org/10.1016/j.jff.2013.08.015.

[2]

Y. Wang, D. Zhang, Y. Liu, et al., The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells, J. Sci. Food Agric. 95 (2015) 936–944, http://dx.doi.org/10.1002/jsfa.6765.

[3]

L. Bell, D.J. Lamport, L.T. Butler, et al., A study of glycaemic effects following acute anthocyanin-rich blueberry supplementation in healthy young adults, Food Funct. 8 (2017) 3104–3110, http://dx.doi.org/10.1039/C7FO00724H.

[4]

S.A. Johnson, A. Figueroa, N. Navaei, et al., Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial, J. Acad. Nutr. Diet. 115 (2015) 369–377, http://dx.doi.org/10.1016/j.jand.2014.11.001.

[5]

Y. Liu, D. Zhang, J. Hu, et al., Visible light-induced lipid peroxidation of unsaturated fatty acids in the retina and the inhibitory effects of blueberry polyphenols, J. Agric. Food Chem. 63 (2015) 9295–9305, http://dx.doi.org/10.1021/acs.jafc.5b04341.

[6]

A. Ghiselli, M. Nardini, A. Baldi, et al., Antioxidant activity of different phenolic fractions separated from an Italian red wine, J. Agric. Food Chem. 46 (2002) 361–367, http://dx.doi.org/10.1021/jf970486b.

[7]

M.L. McCullough, J.J. Peterson, R. Patel, et al., Flavonoid intake and cardiovascular disease mortality in a prospective, Cancer (2012) 454–464, http://dx.doi.org/10.3945/ajcn.111.016634.

[8]

W.C. Liao, Y.C. Lai, M.C. Yuan, et al., Antioxidative activity of water extract ofsweet potato leaves in Taiwan, Food Chem. 127 (2011) 1224–1228.

[9]

G.D. Stoner, L.S. Wang, N. Zikri, et al., Cancer prevention with freeze-dried berries and berry components, Semin. Cancer Biol. 17 (2007) 403–410, http://dx.doi.org/10.1016/j.semcancer.2007.05.001.

[10]

J. Liu, W. Zhang, H. Jing, et al., Bog bilberry (Vaccinium uliginosum L. ) extract reduces cultured hep-g2, caco-2, and 3t3-l1 cell viability, affects cell cycle progression, and has variable effects on membrane permeability, J. Food Sci. 75 (2010), http://dx.doi.org/10.1111/j.1750-3841.2010.01546.x.

[11]

J. Chen, Y. Zhao, X. Tao, et al., Protective effect of blueberry anthocyanins in a CCL4-induced liver cell model, LWT - Food Sci. Technol. 60 (2015) 1105–1112, http://dx.doi.org/10.1080/09540105.2013.781139.

[12]

I. Schönfeld, K. Kraywinkel, Epidemiology of hepatocellular carcinoma in Germany, Onkologe 24 (2018) 653–658.

[13]

J. Bruix, G.J. Gores, V. Mazzaferro, Hepatocellular carcinoma: clinical frontiers and perspectives, Gut 63 (2014) 844–855, http://dx.doi.org/10.1136/gutjnl-2013-306627.

[14]

L. Cicalese, J. Geibel, Hepatocellular carcinoma, MedScape Oncol. (2018) 4–11.

[15]

C. Lu, Z. Liao, M. Cai, et al., MicroRNA-320a downregulation mediates human liver cancer cell proliferation through the Wnt/β-catenin signaling pathway, Oncol. Lett. 13 (2017) 573–578, http://dx.doi.org/10.3892/ol.2016.5479.

[16]

X. Cheng, P. Sun, Q.G. Hu, et al., Transarterial (chemo)embolization for curative resection of hepatocellular carcinoma: a systematic review and meta-analyses, J. Cancer Res. Clin. Oncol. 140 (2014) 1159–1170, http://dx.doi.org/10.1007/s00432-014-1677-4.

[17]

C. Kim, B. Kim, Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: a review, Nutrients 10 (2018), http://dx.doi.org/10.3390/nu10081021.

[18]

L. Zhou, H. Wang, J. Yi, et al., Anti-tumor properties of anthocyanins from Lonicera caerulea 'Beilei' fruit on human hepatocellular carcinoma: in vitro and in vivo study, Biomed. Pharmacother. 104 (2018) 520–529, http://dx.doi.org/10.1016/j.biopha.2018.05.057.

[19]

Y. Li, Z. Yang, S. Jia, et al., Protective effect and mechanism of action of mulberry marc anthocyanins on carbon tetrachloride-induced liver fibrosis in rats, J. Funct. Foods 24 (2016) 595–601, http://dx.doi.org/10.1016/j.jff.2016.05.001.

[20]

J. Zhu, D.Q. Zhu, Y. Zhang, et al., MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene, J. Cell. Physiol. 234 (2019) 2581–2592.

[21]

M.A. O'Brien, R.A. Moravec, L. Riss, Poly (ADP-ribose) polymerase cleavage monitored in situ in apoptotic cells, Biotechniques 30 (2001) 886–891, http://dx.doi.org/10.2144/01304pf01.

[22]

Z. Zhang, Y. Liu, K. Wang, et al., Activation of type 4 metabotropic glutamate receptor promotes cell apoptosis and inhibits proliferation in bladder cancer, J. Cell. Physiol. (2018) 1–15, http://dx.doi.org/10.1002/jcp.27089.

[23]

J. Chen, H. Sun, A. Sun, et al., Studies of the protective effect and antioxidant mechanism of blueberry anthocyanins in a CC14-induced liver injury model in mice, Food Agric. Immunol. 23 (2012) 352–362, http://dx.doi.org/10.1080/09540105.2011.634378.

[24]

Y. Wang, B. Li, Y. Ma, et al., Lonicera caerulea berry extract attenuates lipopolysaccharide induced inflammation in BRL-3A cells: oxidative stress, energy metabolism, hepatic function, J. Funct. Foods 24 (2016) 1–10, http://dx.doi.org/10.1016/j.jff.2016.03.023.

[25]

J. Sun, Y. Wu, C. Long, et al., Anthocyanins isolated from blueberry ameliorates CCl4 induced liver fibrosis by modulation of oxidative stress, inflammation and stellate cell activation in mice, Food Chem. Toxicol. 120 (2018) 491–499, http://dx.doi.org/10.1016/j.fct.2018.07.048.

[26]

K. Roovers, R.K. Assoian, Integrating the MAP kinase signal into the G1 phase cell cycle machinery, Bioessays 22 (9) (2000) 818–826, http://dx.doi.org/10.1002/1521-1878(200009)22:9<818::AID-BIES7>3.0.CO;2-6.

[27]

X. Zhang, X. Wang, T. Wu, et al., Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation, Sci. Rep. 5 (2015) 1–13, http://dx.doi.org/10.1038/srep12579.

[28]

D.Y. Shin, W.S. Lee, J.N. Lu, et al., Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK, Int. J. Oncol. 35 (6) (2009) 1499–1504, http://dx.doi.org/10.3892/ijo00000469.

[29]

F. Musa, B. Pothuri, S.V. Blank, et al., Phase Ⅱ study of irinotecan in combination with bevacizumab in recurrent ovarian cancer, Gynecol. Oncol. 144 (2017) 279–284, http://dx.doi.org/10.1016/j.ygyno.2016.11.043.

[30]

D. Wang, Q. Sun, J. Wu, et al., A new prenylated flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in human hepatocellular carcinoma cells, Sci. Rep. (2017) 1–13, http://dx.doi.org/10.1038/s41598-017-05955-0.

[31]

S.S. Schattauer, A. Bedini, F. Summers, et al., Reactive oxygen species (ROS) generation is stimulated by opioid receptor activation through phosphorylated c-Jun N-terminal kinase and inhibited by p38 mitogen-activated protein kinase (MAPK) activation, J. Biol. Chem. 294 (2019) 16884–16896, http://dx.doi.org/10.1074/jbc.RA119.009592.

[32]

W. Kang, Z. Jia, D. Tang, et al., Fusobacterium nucleatum facilitates apoptosis, ROS generation, and inflammatory cytokine production by activating AKT/MAPK and NF-κ B signaling pathways in human gingival fibroblasts, Oxid. Med. Cell. Longev. (2019), http://dx.doi.org/10.1155/2019/1681972.

[33]

B. Tang, K. Wang, Y.P. Jia, et al., Fusobacterium nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 cells, PLoS One 11 (2016) 1–13, http://dx.doi.org/10.1371/journal.pone.0165701.

[34]

O. Leavy, Inflammation: regulating ROS, Nat. Rev. Immunol. 14 (2014) 357, http://dx.doi.org/10.1038/nri3685.

[35]

A. Rasul, R. Bao, M. Malhi, et al., Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction, Molecules 18 (2013) 1418–1433, http://dx.doi.org/10.3390/molecules18021418.

[36]

X. Chen, X. Hu, Y. Li, et al., Resveratrol inhibits Erk1/2-mediated adhesion of cancer cells via activating PP2A–PTEN signaling network, J. Cell. Physiol. 234 (2019) 2822–2836, http://dx.doi.org/10.1002/jcp.27100.

[37]

E.B. Bian, C. Huang, T.T. Ma, et al., DNMT1-mediated PTEN hypermethylation confers hepatic stellate cell activation and liver fibrogenesis in rats, Toxicol. Appl. Pharmacol. 264 (2012) 13–22, http://dx.doi.org/10.1016/j.taap.2012.06.022.

[38]

J. Á. Fresno Vara, E. Casado, J. de Castro, et al., P13K/Akt signalling pathway and cancer, Cancer Treat. Rev. 30 (2004) 193–204, http://dx.doi.org/10.1016/j.ctrv.2003.07.007.

[39]

J.M.G. Pedrero, D.G. Carracedo, C.M. Pinto, et al., Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma, Int. J. Cancer 114 (2004) 242–248, http://dx.doi.org/10.1002/ijc.20711.

[40]

N. Kramer, A. Walzl, C. Unger, et al., In vitro cell migration and invasion assays, Mutat. Res. - Rev. Mutat. Res. 752 (2013) 10–24, http://dx.doi.org/10.1016/j.mrrev.2012.08.001.

[41]

V. Fathipour, Z. Khaki, S.M. Nassiri, Evaluation of matrix metalloproteinases (MMP)-2 and MMP-9 activity in serum and biochemical and hematological parameters in spontaneous canine cutaneous tumors before and after surgical treatment, Vet. Res. Forum 9 (2018) 19–26.

[42]

J.Y. Park, D.H. Park, Y. Jeon, et al., Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling, Bioorganic Med. Chem. Lett. 28 (2018) 3150–3154, http://dx.doi.org/10.1016/j.bmcl.2018.08.034.

Food Science and Human Wellness
Pages 136-145
Cite this article:
Lin J, Tian J, Shu C, et al. Malvidin-3-galactoside from blueberry suppresses the growth and metastasis potential of hepatocellular carcinoma cell Huh-7 by regulating apoptosis and metastases pathways. Food Science and Human Wellness, 2020, 9(2): 136-145. https://doi.org/10.1016/j.fshw.2020.02.004

526

Views

36

Downloads

27

Crossref

N/A

Web of Science

26

Scopus

0

CSCD

Altmetrics

Received: 04 November 2019
Revised: 03 February 2020
Accepted: 14 February 2020
Published: 15 February 2020
© 2020 "Society information". Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return