BAMLET administration via drinking water inhibits intestinal tumor development and promotes long-term health.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
15 Feb 2024
Historique:
received: 07 11 2023
accepted: 07 02 2024
medline: 16 2 2024
pubmed: 16 2 2024
entrez: 15 2 2024
Statut: epublish

Résumé

Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. Apc

Identifiants

pubmed: 38360830
doi: 10.1038/s41598-024-54040-w
pii: 10.1038/s41598-024-54040-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3838

Subventions

Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360
Organisme : Horizon 2020 Framework Programme
ID : 954360

Informations de copyright

© 2024. The Author(s).

Références

Abbas, Z. & Rehman, S. An overview of cancer treatment modalities. Neoplasm 1, 139–157 (2018).
Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).
doi: 10.3322/caac.21660 pubmed: 33538338
Jasperson, K. W., Patel, S. G. & Ahnen, D. J. APC-associated polyposis conditions. GeneReviews®[Internet] (2017).
Vogelstein, B. et al. Genetic alterations during colorectal-tumor development. New Engl. J. Med. 319, 525–532 (1988).
doi: 10.1056/NEJM198809013190901 pubmed: 2841597
McCart, A. E., Vickaryous, N. K. & Silver, A. Apc mice: Models, modifiers and mutants. Pathol.-Res. Pract. 204, 479–490 (2008).
doi: 10.1016/j.prp.2008.03.004 pubmed: 18538487
Moser, A. R., Pitot, H. C. & Dove, W. F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247, 322–324 (1990).
doi: 10.1126/science.2296722 pubmed: 2296722
The Jackson Laboratory. C57BL/6J-ApcMin/J. https://www.jax.org/strain/002020 (2023).
Mok, K. H., Nagashima, T., Day, I. J., Hore, P. & Dobson, C. M. Multiple subsets of side-chain packing in partially folded states of α-lactalbumins. Proc. Natl. Acad. Sci. 102, 8899–8904 (2005).
doi: 10.1073/pnas.0500661102 pubmed: 15956205 pmcid: 1157025
Pettersson, J., Mossberg, A.-K. & Svanborg, C. α-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem. Biophys. Res. Commun. 345, 260–270 (2006).
doi: 10.1016/j.bbrc.2006.04.081 pubmed: 16678133
Rammer, P. et al. BAMLET activates a lysosomal cell death program in cancer cells. Mol Cancer Therap. 9, 24–32. https://doi.org/10.1158/1535-7163.Mct-09-0559 (2010).
doi: 10.1158/1535-7163.Mct-09-0559
Brinkmann, C. R., Heegaard, C. W., Petersen, T. E., Jensenius, J. C. & Thiel, S. The toxicity of bovine α-lactalbumin made lethal to tumor cells is highly dependent on oleic acid and induces killing in cancer cell lines and noncancer-derived primary cells. FEBS J. 278, 1955–1967 (2011).
doi: 10.1111/j.1742-4658.2011.08112.x pubmed: 21457462
Zhong, S. et al. Cytotoxicity and apoptosis induction of bovine alpha-lactalbumin-oleic acid complex in human breast cancer cells. Food Sci. Technol. Res. 21, 103–110 (2015).
doi: 10.3136/fstr.21.103
Mahanta, S. & Paul, S. Stable self-assembly of bovine α-lactalbumin exhibits target-specific antiproliferative activity in multiple cancer cells. ACS Appl. Mater. Interfaces 7, 28177–28187 (2015).
doi: 10.1021/acsami.5b06076 pubmed: 26440360
Sinevici, N. et al. The novel therapeutic potential of bovine α-lactalbumin made lethal to tumour cells (BALMET) and oleic acid in oral squamous cell carcinoma (OSCC). Eur. J. Cancer Prev. 30, 178–187 (2021).
doi: 10.1097/CEJ.0000000000000617 pubmed: 32694279
HåkanssoN, A., Zhivotovsky, B., Orrenius, S., Sabrarwal, H. & Svanborg, C. Apoptosis induced by a human milk protein. Proc. Natl. Acad. Sci. 92, 8064–8068 (1995).
doi: 10.1073/pnas.92.17.8064 pubmed: 7644538 pmcid: 41287
Pettersson-Kastberg, J. et al. α-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells when in complex with oleic acid: A new biological function resulting from partial unfolding. J. Mol. Biol. 394, 994–1010 (2009).
doi: 10.1016/j.jmb.2009.09.026 pubmed: 19766653
Svensson, M., Håkansson, A., Mossberg, A.-K., Linse, S. & Svanborg, C. Conversion of α-lactalbumin to a protein inducing apoptosis. Proc. Natl. Acad. Sci. 97, 4221–4226. https://doi.org/10.1073/pnas.97.8.4221 (2000).
doi: 10.1073/pnas.97.8.4221 pubmed: 10760289 pmcid: 18203
Duringer, C., Hamiche, A., Gustafsson, L., Kimura, H. & Svanborg, C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J. Biol. Chem. 278, 42131–42135 (2003).
doi: 10.1074/jbc.M306462200 pubmed: 12888554
Svensson, M. et al. α-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human α-lactalbumin made lethal to tumor cells). Prot. Sci. 12, 2794–2804. https://doi.org/10.1110/ps.0231003 (2003).
doi: 10.1110/ps.0231003
Gustafsson, L., Leijonhufvud, I., Aronsson, A., Mossberg, A.-K. & Svanborg, C. Treatment of skin papillomas with topical alpha-lactalbumin-oleic acid. New Engl. J. Med. 350, 2663–2672. https://doi.org/10.1056/NEJMoa032454 (2004).
doi: 10.1056/NEJMoa032454 pubmed: 15215482
Fischer, W. et al. Human α-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res. 64, 2105–2112 (2004).
doi: 10.1158/0008-5472.CAN-03-2661 pubmed: 15026350
Mossberg, A. K. et al. Bladder cancers respond to intravesical instillation of (HAMLET human α-lactalbumin made lethal to tumor cells). Int. J. Cancer 121, 1352–1359 (2007).
doi: 10.1002/ijc.22810 pubmed: 17514650
Mossberg, A.-K., Hou, Y., Svensson, M., Holmqvist, B. & Svanborg, C. HAMLET treatment delays bladder cancer development. J. Urol. 183, 1590–1597 (2010).
doi: 10.1016/j.juro.2009.12.008 pubmed: 20172551
Puthia, M., Storm, P., Nadeem, A., Hsiung, S. & Svanborg, C. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells). Gut 63, 131–142 (2014).
doi: 10.1136/gutjnl-2012-303715 pubmed: 23348960
Brisuda, A. et al. Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex. Nat. Commun. 12, 1–16 (2021).
doi: 10.1038/s41467-021-23748-y
Su, L.-K. et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256, 668–670 (1992).
doi: 10.1126/science.1350108 pubmed: 1350108
Stenhouse, G., Fyfe, N., King, G., Chapman, A. & Kerr, K. Thyroid transcription factor 1 in pulmonary adenocarcinoma. J. Clin. Pathol. 57, 383–387 (2004).
doi: 10.1136/jcp.2003.007138 pubmed: 15047742 pmcid: 1770279
Hien, T. T. et al. Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy. Int. J. Cancer 1, 1 (2023).
Hansen, J. S. et al. Peptide–oleate complexescreate novel membrane-bound compartments. Mol. Biol. Evol. 37, 3083–3093 (2020).
doi: 10.1093/molbev/msaa138 pubmed: 32521018
Brest, P. et al. Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer research 67, 11327–11334 (2007).
doi: 10.1158/0008-5472.CAN-07-1153 pubmed: 18056459
Storm, P. et al. Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis. Oncogene 30, 4765–4779 (2011).
doi: 10.1038/onc.2011.196 pubmed: 21643007 pmcid: 4041205
Halberg, R. B. et al. Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway. Cancer Res. 69, 5768–5775 (2009).
doi: 10.1158/0008-5472.CAN-09-0446 pubmed: 19584276 pmcid: 2775466
Königshoff, M. et al. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PloS One 3, e2142 (2008).
doi: 10.1371/journal.pone.0002142 pubmed: 18478089 pmcid: 2374879
Wong, R. P., Hwang, W. S. & Field, S. K. Familial adenomatous polyposis and lung cancer. J. Surg. Oncol. 60, 213–214 (1995).
doi: 10.1002/jso.2930600314 pubmed: 7475074
Yamaguchi, M. & Takai, S. Chronic Administration of bovine milk-derived α-lactalbumin improves glucose tolerance via enhancement of adiponectin in goto–kakizaki rats with type 2 diabetes. Biol. Pharm. Bull. 37, 404–408 (2014).
doi: 10.1248/bpb.b13-00762 pubmed: 24583859
Gao, J., Song, J., Du, M. & Mao, X. Bovine α-lactalbumin hydrolysates (α-LAH) ameliorate adipose insulin resistance and inflammation in high-fat diet-fed C57BL/6J mice. Nutrients 10, 242 (2018).
doi: 10.3390/nu10020242 pubmed: 29473848 pmcid: 5852818
Boscaini, S. et al. Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice. Br. J. Nutrit. 121, 1097–1107 (2019).
doi: 10.1017/S0007114519000461
Brahmer, J. R. et al. Safety and activity of anti–PD-L1 antibody in patients with advanced cancer. New Engl. J. Med. 366, 2455–2465 (2012).
doi: 10.1056/NEJMoa1200694 pubmed: 22658128
Hu, H. et al. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial. Lancet Gastroenterol. Hepatol. 7, 38–48 (2022).
doi: 10.1016/S2468-1253(21)00348-4 pubmed: 34688374
Le, D. T. et al. PD-1 blockade in tumors with mismatch-repair deficiency. New Engl. J. Med. 372, 2509–2520. https://doi.org/10.1056/NEJMoa1500596 (2015).
doi: 10.1056/NEJMoa1500596 pubmed: 26028255
Patsoukis, N., Wang, Q., Strauss, L. & Boussiotis, V. A. Revisiting the PD-1 pathway. Sci. Adv. 6, ea2712 (2020).
doi: 10.1126/sciadv.abd2712
Stacey, A. et al. Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice. Proc. Natl. Acad. Sci. 92, 2835–2839. https://doi.org/10.1073/pnas.92.7.2835 (1995).
doi: 10.1073/pnas.92.7.2835 pubmed: 7708733 pmcid: 42313
Wijesinha-Bettoni, R., Dobson, C. M. & Redfield, C. Comparison of the structural and dynamical properties of holo and apo bovine α-lactalbumin by NMR spectroscopy. J. Mol. Biol. 307, 885–898 (2001).
doi: 10.1006/jmbi.2001.4530 pubmed: 11273708
Krämer, A., Green, J., Pollard, J. Jr. & Tugendreich, S. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30, 523–530 (2014).
doi: 10.1093/bioinformatics/btt703 pubmed: 24336805

Auteurs

Hien Thi Tran (HT)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Murphy Lam Yim Wan (MLY)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Ines Ambite (I)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Michele Cavalera (M)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Mario Grossi (M)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Jaromir Háček (J)

Department of Pathology and Molecular Medicine, Motol University Hospital, 2nd Faculty of Medicine, Charles University Praha, 150 06, Prague, Czech Republic.

Parisa Esmaeili (P)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

António N B M Carneiro (ANBM)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Arunima Chaudhuri (A)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Shahram Ahmadi (S)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden.

Catharina Svanborg (C)

Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Klinikgatan 28, 221 84, Lund, Sweden. catharina.svanborg@med.lu.se.

Classifications MeSH