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Research Article | Open Access

Lunasin peptide promotes lysosome-mitochondrial mediated apoptosis and mitotic termination in MDA-MB-231 cells

Yuqiong Haoa,b,1, Huimin Guoc,1, Yechun Hongb, Xin Fana, Yumei Sud, Xiushi Yange( ), Guixing Rena
Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Institute of Plant and Food Science, Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China
Biotechnology Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
College of Life Sciences, Xinjiang Agricultural University, Urumqi 830001, China
Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

1 These authors have contributed equally to this work.

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

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Abstract

Lunasin, a novel bioactive peptide, is well-known for its anti-proliferation activity. However, the mechanism of this effect is still poorly reported. Here, synthesized lunasin was used and its anti-proliferative function was observed at the concentration of 0.25 mg/mL in human breast cancer cell MDA-MB-231. Conjoint analysis of transcriptome and proteome of MDA-MB-231cells was further performed. The results demonstrated that cysteinyl aspartate specific proteinase (CASP) 3, CASP 7, and CASP 14 were significantly up-regulated after lunasin exposure, together with an increased Bax/Bcl-2 ratio from 22.9 to 210.6, which indicated that caspase-mediated mitochondria intrinsic apoptosis was highly activated. Moreover, lysosomal pathway was significantly suppressed under lunasin exposure, suggesting that lysosome may cooperate with mitochondria to participate in apoptosis. In addition, lunasin also down-regulated genes involved in DNA replication in MDA-MB-231 cells. Overall, our study reveals that the anti-proliferation effect of lunasin peptide might be triggered via the inhibition of DNA replication and cell mitosis, as well as the promotion of lysosome-mitochondrial mediated cell apoptosis.

Keywords

DNA replicationAnti-proliferationCell apoptosisTranscriptome and proteome analysis

References

[1]

L.M. Coussens, Z. Werb, Inflammation and cancer, Nature 420 (2002) 860-867. https://doi.org/10.1038/nature01322.
Crossref Google Scholar
[2]

D.E. Khoury, C. Cuda, B.L. Luhovyy, et al., Beta glucan: health benefits in obesity and metabolic syndrome, J. Nutr. Metab. 2012 (2012) 851362-851389. https://doi.org/10.1155/2012/851362.
Crossref Google Scholar
[3]

J.A. Deluca, E.L. Garcia-Villatoro, C.D. Allred, Flaxseed bioactive compounds and colorectal cancer prevention, Curr. Oncol. Rep. 20 (2018) 59. https://doi.org/10.1007/s11912-018-0704-z.
Crossref Google Scholar
[4]

B. Hernandez-Ledesma, C.C. Hsieh, B.O. de Lumen, Chemopreventive properties of peptide lunasin: a review, Protein Pept. Lett. 20 (2013) 424-432. https://doi.org/10.2174/092986613805290327.
Crossref Google Scholar
[5]

J. Liu, S.H. Jia, M. Kirberger, et al., Lunasin as a promising health-beneficial peptide, Eur. Rev. Med. Pharmacol. Sci. 18 (2014) 2070-2075. https://doi.org/10.4314/tjpr.v13i7.24.
Crossref Google Scholar
[6]

E.G. de Mejia, V.P. Dia, Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-κB pathway in the macrophage, Peptides 30 (2009) 2388-2398. https://doi.org/10.1016/j.peptides.2009.08.005.
Crossref Google Scholar
[7]

B. Hernandez-Ledesma, C.C. Hsieh, B.O. de Lumen, Lunasin, a novel seed peptide for cancer prevention, Peptides 30 (2009) 426-430. https://doi.org/10.1016/j.peptides.2008.11.002.
Crossref Google Scholar
[8]

B. Hernández-Ledesma, C.C. Hsieh, B.O. de Lumen, Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW264.7 macrophages, Biochem. Biophys. Res. Commun. 390 (2009) 803-808. https://doi.org/10.1016/j.bbrc.2009.10.053.
Crossref Google Scholar
[9]

C.C. Hsieh, Y.F. Wang, P.Y. Lin, et al., Seed peptide lunasin ameliorates obesity-induced inflammation and regulates immune responses in C57BL/6J mice fed high-fat diet, Food Chem. Toxicol. 147 (2021) 111908. https://doi.org/10.1016/j.fct.2020.111908.
Crossref Google Scholar
[10]

G. Ren, Y. Hao, Y. Zhu, et al., Expression of bioactive lunasin peptide in transgenic rice grains for the application in functional food, Molecules 23 (2018) 2373. https://doi.org/10.3390/molecules23092373.
Crossref Google Scholar
[11]

S. Fernández-Tomé, P. Indiano-Romacho, I. Mora-Gutiérrez, et al., Lunasin peptide is a modulator of the immune response in the human gastrointestinal tract, Mol. Nutr. Food Res. 65 (2021) 2001034. https://doi.org/10.1002/mnfr.202001034.
Crossref Google Scholar
[12]

H.J. Jeong, J.B. Jeong, D.S. Kim, et al., The cancer preventive peptide lunasin from wheat inhibits core histone acetylation, Cancer Lett. 255 (2007) 42-48. https://doi.org/10.1016/j.canlet.2007.03.022.
Crossref Google Scholar
[13]

V.P. Dia, E.G. de Mejia, Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression, Cancer Lett. 295 (2010) 44-53. https://doi.org/10.1016/j.canlet.2010.02.010.
Crossref Google Scholar
[14]

C.C. Hsieh, B. Hernádez-Ledesma, B.O. de Lumen, Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable, PLoS ONE 5 (2010) e8890. https://doi.org/10.1371/journal.pone.0008890.
Crossref Google Scholar
[15]

B. Hernández-Ledesma, C.C. Hsieh, B.O. de Lumen, Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation, Mol. Nutr. Food Res. 55 (2011) 989-998. https://doi.org/10.1002/mnfr.201000632.
Crossref Google Scholar
[16]

A.F. Galvez, N. Chen, J. Macasieb, et al., Chemopreventive property of a soybean peptide (lunasin) that binds to deacetylated histones and inhibits acetylation, Cancer Res. 61 (2001) 7473-7478. https://doi.org/10.1016/S0165-4608(01)00475-7.
Crossref Google Scholar
[17]

P. Singh, K. Bisetty, A molecular dynamics study of lunasin, S. Afr. J. Chem. 65 (2012) 115-124. https://doi.org/10.1002/jctb.2690.
Crossref Google Scholar
[18]

K.J. Karczewski, M.P. Snyder, Integrative omics for health and disease, Nat. Rev. Genet. 19 (2018) 299-310. https://doi.org/10.1038/nrg.2018.4.
Crossref Google Scholar
[19]

Z.Q. Liu, T. Mahmood, P.C. Yang, Western blot: technique, theory and troubleshooting, N. Am. J. Med. Sci. 4 (2014) 429-434. https://doi.org/10.4103/1947-2714.128482.
Crossref Google Scholar
[20]

Y. Zhu, Z. Shi, Y. Yao, et al., Antioxidant and anti-cancer activities of proanthocyanidins-rich extracts from three varieties of sorghum (Sorghum bicolor) bran, Food Agric. Immunol. 28 (2017) 1-14. https://doi.org/10.1080/09540105.2017.1351526.
Crossref Google Scholar
[21]

W. Zhang, Y. Hao, C. Ten, et al., Effects of salt stimulation on lunasin accumulation and activity during soybean germination, Foods 9 (2020) 118. https://doi.org/10.3390/foods9020118.
Crossref Google Scholar
[22]

C.C. Hsieh, B. Hernández-Ledesma, B.O. de Lumen, Cell proliferation inhibitory and apoptosis inducing properties of anacardic acid and lunasin in human breast cancer MDA-MB-231 cells, Food Chem. 125 (2011) 630-636. https://doi.org/10.1016/j.foodchem.2010.09.051.
Crossref Google Scholar
[23]

E.J. McConnell, B. Devapatla, K. Yaddanapudi, et al., The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell proliferation by suppressing phosphorylation of the retinoblastoma protein, Oncotarget 6 (2015) 4649-4662. https://doi.org/10.18632/oncotarget.3080.
Crossref Google Scholar
[24]

V.P. Dia, E.G. de Mejia, Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells, Mol. Nutr. Food Res. 55 (2011) 623-634. https://doi.org/10.1002/mnfr.201000419.
Crossref Google Scholar
[25]

C.C. Hsieh, C. Martínez-Villaluenga, B.O. de Lumen, et al., Updating the research on the chemopreventive and therapeutic role of the peptide lunasin, J. Agric. Food Sci. 98 (2018) 2070-2079. https://doi.org/10.1002/jsfa.8719.
Crossref Google Scholar
[26]

B. Chen, H. Li, X. Zeng, et al., Roles of microRNA on cancer cell metabolism, J. Transl. Med. 10 (2012) 1-12. https://doi.org/10.1186/1479-5876-10-228.
Crossref Google Scholar
[27]

V. Villard, O. Kalvuzhniv, O. Riccio, et al., Synthetic RGD-containing alphahelical coiled coil peptides promote integrin-dependent cell adhesion, J. Pept. Sci. 12 (2006) 206-212. https://doi.org/10.1002/psc.707.
Crossref Google Scholar
[28]

X. Lu, D. Lu, M.F. Scully, et al., Integrins in drug targeting-RGD templates in toxins, Curr. Pharm. Des. 12 (2006) 2749-2769. https://doi.org/10.2174/138161206777947713.
Crossref Google Scholar
[29]

K. Matsuki, T. Sasho, K. Nakagawa, et al., RGD peptide-induced cell death of chondrocytes and synovial cells, J. Orthop. Sci. 13 (2008) 524-532. https://doi.org/10.1007/s00776-008-1281-z.
Crossref Google Scholar
[30]

X. Fan, P. Qin, Y. Hao, et al., Overexpression of soybean-derived lunasin in wheat and assessment of its anti-proliferative activity in colorectal cancer HT-29 cells, Int. J. Mol. Sci. 21 (2020) 24. https://doi.org/10.3390/ijms21249594.
Crossref Google Scholar
[31]

C. Wang, S. Li, H. Ren, et al., Anti-proliferation and pro-apoptotic effects of diosmetin via modulating cell cycle arrest and mitochondria-mediated intrinsic apoptotic pathway in MDA-MB-231 cells, Med. Sci. Monit. 25 (2019) 4639-4647. https://doi.org/25:4639-4647.
Crossref Google Scholar
[32]

S. Lang, L. Huang, The sulfolobus solfataricus GINS complex stimulates DNA binding and processive DNA unwinding by minichromosome maintenance helicase, J. Bacteriol. 197 (2015) 3409-3420. https://doi.org/10.1128/JB.00496-15.
Crossref Google Scholar
[33]

M. Muzi-Falconi, M. Giannattasio, M. Foiani, et al., The DNA polymerase alpha-primase complex: multiple functions and interactions, Sci. World J. 3 (2003) 21-33. https://doi.org/10.1100/tsw.2003.05.
Crossref Google Scholar
[34]

A.F. Galvez, B.O. de Lumen, A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells, Nat. Biotechnol. 17 (1999) 495-500. https://doi.org/10.1038/8676.
Crossref Google Scholar
[35]

H.J. Jeong, J.B. Jeong, D.S. Kim, et al., Inhibition of core histone acetylation by the cancer preventive peptide lunasin, J. Agric. Food Chem. 55 (2007) 632-637. https://doi.org/10.1021/jf062405u.
Crossref Google Scholar
[36]

E. Maldonado-Cervantes, H.J. Jeong, F. Leon-Galvan, et al., Amaranth lunasin peptide internalizes into the cell nucleus and inhibits chemical carcinogen-induced transformation of NIH-3T3 cells, Peptides 31 (2010) 1635-1642. https://doi.org/10.1016/j.peptides.2010.06.014.
Crossref Google Scholar
[37]

W.A. Dunn, Autophagy and related mechanisms of lysosome-mediated protein degradation, Trends Cell Biol. 4 (1994) 139-143. https://doi.org/10.1016/0962-8924(94)90069-8.
Crossref Google Scholar
[38]

S. Kornfeld, I. Mellman, The biogenesis of lysosomes, Annu. Rev. Cell Biol. 5 (1989) 483-525. https://doi.org/10.1146/annurev.cb.05.110189.002411.
Crossref Google Scholar
[39]

P. Saftig, J. Klumperman, Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function, Nat. Rev. Mol. Cell Biol. 10 (2009) 623-635. https://doi.org/10.1038/nrm2745.
Crossref Google Scholar
[40]

C. Settembre, A. Fraldi, D.L. Medina, et al., Signals from the lysosome: a control centre for cellular clearance and energy metabolism, Nat. Rev. Mol. Cell Biol. 14 (2013) 283-296. https://doi.org/10.1038/nrm3565.
Crossref Google Scholar
[41]

C.T. Hua, J.J. Hopwood, S.R. Carlsson, et al., Evaluation of the lysosome-associated membrane protein LAMP-2 as a marker for lysosomal storage disorders, Clin. Chem. 44 (1998) 2094-2102. https://doi.org/10.1093/clinchem/44.10.2094.
Crossref Google Scholar
[42]

K. Gumpper, M. Sermersheim, M.X. Zhu, et al., Skeletal muscle lysosomal function via cathepsin activity measurement, Methods Mol. Biol. 1854 (2019) 35-43. https://doi.org/10.1007/7651_2017_64.
Crossref Google Scholar
[43]

S.M. Man, T.D. Kanneganti, Regulation of lysosomal dynamics and autophagy by CTSB/cathepsin B, Autophagy 12 (2016) 2504-2505. https://doi.org/10.1080/15548627.2016.1239679.
Crossref Google Scholar
[44]

S. Ivanova, U. Repnik, L. Bojic, et al., Lysosomes in apoptosis, Methods Enzymol. 442 (2008) 183-199. https://doi.org/10.1016/S0076-6879(08)01409-2.
Crossref Google Scholar
[45]

X. Fan, G. Luo, D. Yang, et al., Critical role of lysosome and its associated protein cathepsin D in manganese-induced toxicity in cultured midbrain astrocyte, Neurochem. Int. 56 (2010) 291-300. https://doi.org/10.1016/j.neuint.2009.11.001.
Crossref Google Scholar
[46]

Z. Chen, B. Wang, F. Yu, et al., The roles of mitochondria in radiation-induced autophagic cell death in cervical cancer cells, Tumour. Biol. 37 (2016) 4083-4091. https://doi.org/10.1007/s13277-015-4190-8.
Crossref Google Scholar
[47]

A. Terman, B. Gustafsson, U. Brunk, The lysosomal-mitochondrial axis theory of postmitotic aging and cell death, Chem. Biol. Interact. 163 (2006) 29-37. https://doi.org/10.1016/j.cbi.2006.04.013.
Crossref Google Scholar
Food Science and Human Wellness
Volume 11 Issue 6,
November 2022
Pages 1598-1606
DOI: 10.1016/j.fshw.2022.06.018
Cite this article:
Hao Y, Guo H, Hong Y, et al. Lunasin peptide promotes lysosome-mitochondrial mediated apoptosis and mitotic termination in MDA-MB-231 cells. Food Science and Human Wellness, 2022, 11(6): 1598-1606. https://doi.org/10.1016/j.fshw.2022.06.018

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Received: 11 April 2021
Revised: 31 May 2021
Accepted: 13 August 2021
Published: 18 July 2022
© 2022 Beijing Academy of Food Sciences.

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