Skip to main content

Advertisement

SpringerLink
Log in

LvHemB1, a novel cationic antimicrobial peptide derived from the hemocyanin of Litopenaeus vannamei, induces cancer cell death by targeting mitochondrial voltage-dependent anion channel 1

  • Original Article
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Current cancer treatment regimens such as chemotherapy and traditional chemical drugs have adverse side effects including the appearance of drug-resistant tumor cells. For these reasons, it is imperative to find novel therapeutic agents that overcome these factors. To this end, we explored a cationic antimicrobial peptide derived from Litopenaeus vannamei hemocyanin (designated LvHemB1) that induces cancer cell death, but sparing normal cells. LvHemB1 inhibits the proliferation of human cervical (HeLa), esophageal (EC109), hepatocellular (HepG2), and bladder (EJ) cancer cell lines, but had no significant effect on normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE-3) cells). In addition to its antiproliferative effects, LvHemB1 induced apoptosis, by permeating cells and targeting mitochondrial voltage-dependent anion channel 1 (VDAC1). Colocalization studies revealed the localization of LvHemB1 in mitochondria, while molecular docking and pull-down analyses confirmed LvHemB1-VDAC1 interaction. Moreover, LvHemB1 causes loss in mitochondrial membrane potential and increases levels of reactive oxygen species (ROS) and apoptotic proteins (caspase-9, caspase-3, and Bax (Bcl-2-associated X)), which results in mitochondrial-mediated apoptosis. Thus, peptide LvHemB1 has the potential of being used as an anticancer agent due to its antiproliferation effect and targeting to VDAC1 to cause mitochondrial dysfunction in cancer cells, as well as its ability to induce apoptosis by increasing ROS levels, and the expression of proapoptotic proteins.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The datasets used are available from the corresponding authors on request.

References

  • Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281:1322–6.

    Article  CAS  PubMed  Google Scholar 

  • Baker MA, Maloy WL, Zasloff M, Jacob LS. Anticancer efficacy of Magainin2 and analogue peptides. Cancer Res. 1993;53:3052–7.

    CAS  PubMed  Google Scholar 

  • Balasubramanian K, Schroit AJ. Aminophospholipid asymmetry: a matter of life and death. Annu Rev Physiol. 2003;65:701–34.

    Article  CAS  PubMed  Google Scholar 

  • Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 2011;476:341–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baxter AA, Lay FT, Poon IKH, Kvansakul M, Hulett MD. Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects. Cell Mol Life Sci. 2017;74:3809–25.

    Article  CAS  PubMed  Google Scholar 

  • Bevers EM, Comfurius P, Zwaal RF. Regulatory mechanisms in maintenance and modulation of transmembrane lipid asymmetry: pathophysiological implications. Lupus. 1996;5:480–7.

    Article  CAS  PubMed  Google Scholar 

  • Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005;3:238–50.

    Article  CAS  PubMed  Google Scholar 

  • Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29:222–30.

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.

    Article  PubMed  Google Scholar 

  • Coates CJ, Decker H. Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin. Cell Mol Life Sci. 2017;74:293–317.

    Article  CAS  PubMed  Google Scholar 

  • Coates CJ, Nairn J. Diverse immune functions of hemocyanins. Dev Comp Immunol. 2014;45:43–55.

    Article  CAS  PubMed  Google Scholar 

  • Coin I, Beyermann M, Bienert M. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nat Protoc. 2007;2:3247–56.

    Article  CAS  PubMed  Google Scholar 

  • De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011;476:336–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Decker H, Rimke T. Tarantula hemocyanin shows phenoloxidase activity. J Biol Chem. 1998;273:25889–92.

    Article  CAS  PubMed  Google Scholar 

  • Dehart DN, Fang D, Heslop K, Heslop K, Li L, Lemasters JJ, et al. Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. Biochem Pharmcaol. 2018;148:155–62.

    Article  CAS  Google Scholar 

  • Destoumieux-Garzón D, Saulnier D, Garnier J, Jouffrey C, Bulet P, Bachère E. Crustacean immunity: antifungal peptides are generated from the C terminus of shrimp hemocyanin in response to microbial challenge. J Biol Chem. 2001;276:47070–7.

    Article  PubMed  Google Scholar 

  • Dobrzyńska I, Szachowicz-Petelska B, Sulkowski S, Figaszewski Z. Changes in electric charge and phospholipids composition in human colorectal cancer cells. Mol Cell Biochem. 2005;276:113–9.

    Article  PubMed  CAS  Google Scholar 

  • Epand RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta. 1999;1462:11–28.

    Article  CAS  PubMed  Google Scholar 

  • Fox JL. Antimicrobial peptides stage a comeback. Nat Biotechnol. 2013;31:379–82.

    Article  CAS  PubMed  Google Scholar 

  • Gaspar D, Castanho MARB. Anticancer peptides: prospective innovation in cancer therapy. Springer International Publishing. 2016; 95-109.

  • Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–12.

    Article  CAS  PubMed  Google Scholar 

  • Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science. 2011;333:1109–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hancock RE. Peptide antibiotics. Lancet. 1997;349:418–22.

    Article  CAS  PubMed  Google Scholar 

  • Heslop KA, Rovini A, Hunt EG, Fang D, Morris ME, Christie CF, et al. JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells. Biochem Pharmacol. 2020;171:113728.

    Article  CAS  PubMed  Google Scholar 

  • Hilchie AL, Doucette CD, Pinto DM, Patrzykat A, Douglas S, Hoskin DW. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts. Breast Cancer Res. 2011;13:R102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huertas NJ, Monroy ZJR, Medina RF, Castañeda JEG. Antimicrobial activity of truncated and polyvalent peptides derived from the FKCRRQWQWRMKKGLA sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Molecules. 2017;22:987.

    Article  PubMed Central  CAS  Google Scholar 

  • Jaenicke E, Föll R, Decker H. Spider hemocyanin binds ecdysone and 20-OH-ecdysone. J Biol Chem. 1999;274:34267–71.

    Article  CAS  PubMed  Google Scholar 

  • Jin XB, Wang YJ, Liang LL, Pu QH, Shen J, Lu XM, et al. Cecropin suppresses human hepatocellular carcinoma BEL-7402 cell growth and survival in vivo without side-toxicity. Asian Pac J Cancer Prev. 2014;15:5433–6.

    Article  PubMed  Google Scholar 

  • Klein MJ, Schmidt S, Wadhwani P, Bürck J, Reichert J, Afonin S, et al. Lactam-stapled cell-penetrating peptides: cell uptake and membrane binding properties. J Med Chem. 2017;60:8071–82.

    Article  CAS  PubMed  Google Scholar 

  • Kong LR, Chua KN, Sim WJ, Ng HC, Bi C, Ho J, et al. MEK inhibition overcomes cisplatin resistance conferred by SOS/MAPK pathway activation in squamous cell carcinoma. Mol Cancer Ther. 2015;14:1750–60.

    Article  CAS  PubMed  Google Scholar 

  • Koo CY, Sen YP, Bay BH, Yip GW. Targeting heparan sulfate proteoglycans in breast cancer treatment. Recent Pat Anticancer Drug Discov. 2008;3:151–8.

    Article  CAS  PubMed  Google Scholar 

  • Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009;9:874–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leanza L, Romio M, Becker KA, Azzolini M, Trentin L, Managò A, et al. Direct pharmacological targeting of a mitochondrial ion channel selectively kills tumor cells in vivo. Cancer Cell. 2017;31:516–31.

    Article  CAS  PubMed  Google Scholar 

  • Lee SY, Lee BL, Söderhäll K. Processing of an antibacterial peptide from hemocyanin of the freshwater crayfish Pacifastacus leniusculus. J Biol Chem. 2003;278:7927–33.

    Article  CAS  PubMed  Google Scholar 

  • Li C, Zhu J, Wang Y, Chen Y, Song L, Zheng W, et al. Antibacterial activity of AI-Hemocidin 2, a novel N-terminal peptide of hemoglobin purified from Arca inflata. Mar Drugs. 2017;15:205.

    Article  CAS  PubMed Central  Google Scholar 

  • Li Y, Li L, Chen M, Yu X, Gu Z, Qiu H, et al. MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and degradation. Mol Oncol. 2018;12:391–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu SJ, Zheng LY, Aweya JJ, Zheng Z, Zhong MQ, Chen JH, et al. Litopenaeus vannamei hemocyanin exhibits antitumor activity in S180 mouse model in vivo. PLoS One. 2017;12:e0183783.

  • Liu SJ, Aweya JJ, Zheng LY, Wang F, Zheng Z, Zhong MQ, et al. A Litopenaeus vannamei hemocyanin-derived antimicrobial peptide (peptide B11) attenuates cancer cells' proliferation. Molecules. 2018;23:3202.

    Article  PubMed Central  CAS  Google Scholar 

  • Mader JS, Hoskin DW. Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs. 2006;15:933–46.

    Article  CAS  PubMed  Google Scholar 

  • Mader JS, Salsman J, Conrad DM, Hoskin DW. Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Mol Cancer Ther. 2005;4:612–4.

    Article  CAS  PubMed  Google Scholar 

  • Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–89.

    Article  PubMed  Google Scholar 

  • Mottis A, Herzig S, Auwerx J. Mitocellular communication: shaping health and disease. Science. 2019;366:827–32.

    Article  CAS  PubMed  Google Scholar 

  • Mulder KC, Lima LA, Miranda VJ, Dias SC, Franco OL. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides. Front Microbiol. 2013;4:321.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nesterova NV, Zagorodnya SD, Moshtanska V, Dolashka P, Baranova GV, Golovan AV, et al. Antiviral activity of hemocyanin isolated from marine snail Rapana venosa. Antivir Res. 2011;90:A38.

    Article  Google Scholar 

  • O’Brien-Simpson NM, Hoffmann R, Chia CSB, Wade JD. Editorial: antimicrobial and anticancer peptides. Front Chem. 2018;6:13.

    Article  PubMed  PubMed Central  Google Scholar 

  • Paul RJ, Pirow R. The physiological significance of respiratory proteins in invertebrates. Zoology. 1997;100:298–306.

    Google Scholar 

  • Petit VW, Rolland JL, Blond A, Cazevieille C, Djediat C, Peduzzi J, et al. A hemocyanin-derived antimicrobial peptide from the penaeid shrimp adopts an alpha-helical structure that specifically permeabilizes fungal membranes. Biochim Biophys Acta. 2016;1860:557–68.

    Article  CAS  PubMed  Google Scholar 

  • Pushpanathan M, Gunasekaran P, Rajendhran J. Antimicrobial peptides: versatile biological properties. Int J Pept. 2013;2013:675391.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qiao J, Du ZH, Zhang YL, Du H, Guo LL, Zhong MQ, et al. Proteomic identification of the related immune-enhancing proteins in shrimp Litopenaeus vannamei stimulated with vitamin C and Chinese herbs. Fish Shellfish Immunol. 2011;31:736–45.

    Article  CAS  PubMed  Google Scholar 

  • Raman K, Kuberan B. Chemical tumor biology of heparan sulfate proteoglycans. Curr Chem Biol. 2010;4:20–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ran S, Thorpe PE. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy. Int J Radiat Oncol Biol Phys. 2002;54:1479–84.

    Article  CAS  PubMed  Google Scholar 

  • Riedl S, Zweytick D, Lohner K. Membrane-active host defense peptides – challenges and perspectives for the development of novel anticancer drugs. Chem Phys Lipids. 2011;164:766–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues EG, Dobroff AS, Cavarsan CF, Paschoalin T, Nimrichter L, Mortara RA, et al. Effective topical treatment of subcutaneous murine B16F10-Nex2 melanoma by the antimicrobial peptide gomesin. Neoplasia. 2008;10:61–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roudi R, Syn NL, Roudbary M. Antimicrobial peptides as biologic and immunotherapeutic agents against cancer: a comprehensive overview. Front Immunol. 2017;8:1320.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shoshan-Barmatz V, Mizrachi D, Keinan N. Oligomerization of the mitochondrial protein VDAC1: from structure to function and cancer therapy. Prog Mol Biol Transl Sci. 2013;117:303–34.

    Article  CAS  PubMed  Google Scholar 

  • Shoshan-Barmatz V, Krelin Y, Shteinfer-Kuzmine A, Arif T. Voltage-dependent anion channel 1 as an emerging drug target for novel anti-cancer therapeutics. Front Oncol. 2017;7:154.

    Article  PubMed  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.

    Article  PubMed  Google Scholar 

  • Stark M, Liu LP, Deber CM. Cationic hydrophobic peptides with antimicrobial activity. Antimicrob Agents Chemother. 2002;46:3585–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tassanakajon A, Rimphanitchayakit V, Visetnan S, Amparyup P, Somboonwiwat K, Charoensapsri W, et al. Shrimp humoral responses against pathogens: antimicrobial peptides and melanization. Dev Comp Immunol. 2018;80:81–93.

    Article  CAS  PubMed  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  • Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vega LA, Caparon MG. Cationic antimicrobial peptides disrupt the Streptococcus pyogenes ExPortal. Mol Microbiol. 2012;85:1119–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, et al. Superoxide flashes in single mitochondria. Cell. 2008;134:279–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Ma JL, Yang YG, Song Y, Wu J, Qin YY, et al. Efficient therapeutic delivery by a novel cell-permeant peptide derived from KDM4A protein for antitumor and antifibrosis. Oncotarget. 2016;7:49075–90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang X, Chen C, Zhou G, Ye J, Yin R, Feng D, et al. Sepia ink oligopeptide induces apoptosis of lung cancer cells via mitochondrial pathway. Cell Physiol Biochem. 2018;45:2095–106.

    Article  CAS  PubMed  Google Scholar 

  • Wu Q, Yang Z, Nie Y, Shi Y, Fan D. Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches. Cancer Lett. 2014;347:159–66.

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Zhang H, Qi W, Zhang Y, Li J, Li Z, et al. Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis. 2018;9:171.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wysocka J. Identifying novel proteins recognizing histone modifications using peptide pull-down assay. Methods. 2006;40:339–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan F, Zhang YL, Jiang RP, Zhong MQ, Hu Z, Du H, et al. Identification and agglutination properties of hemocyanin from the mud crab (Scylla serrata). Fish Shellfish Immunol. 2011;30:354–60.

    Article  CAS  PubMed  Google Scholar 

  • Yang S, Huang H, Wang F, Aweya JJ, Zheng ZH, Zhang YL. Prediction and characterization of a novel hemocyanin-derived antimicrobial peptide from shrimp Litopenaeus vannamei. Amino Acids. 2018;50:995–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi Y, You X, Bian C, Chen S, Lv Z, Qiu L, et al. High-throughput identification of antimicrobial peptides from amphibious mudskippers. Mar Drugs. 2017;15:364.

    Article  PubMed Central  CAS  Google Scholar 

  • Zhang YL, Wang SY, Peng XX. Identification of a type of human IgG-like protein in shrimp Penaeus vannamei by mass spectrometry. J Exp Mar Biol Ecol. 2004;301:39–54.

    Article  CAS  Google Scholar 

  • Zhang YL, Wang SY, Xu AL, Chen J, Lin BK, Peng XX. Affinity proteomic approach for identification of an IgA-like protein in Litopenaeus vannamei and study on its agglutination characterization. J Proteome Res. 2006;5:815–21.

    Article  CAS  PubMed  Google Scholar 

  • Zhang YL, Yan F, Hu Z, Zhao XL, Min SY, Du ZH, et al. Hemocyanin from shrimp Litopenaeus vannamei shows hemolytic activity. Fish Shellfish Immunol. 2009;27:330–5.

    Article  PubMed  CAS  Google Scholar 

  • Zheng LY, Zhao XL, Zhang P, Chen CD, Liu SJ, Huang R, et al. Hemocyanin from shrimp Litopenaeus vannamei has antiproliferative effect against HeLa cell in vitro. PLoS One. 2016;11:e0151801.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu L, Yuan H, Guo C, Lu Y, Deng S, Yang Y, et al. Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway. J Cell Physiol. 2012;227:1814–20.

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Dean AE, Horikoshi N, Heer C, Spitz DR, Gius D. Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy. J Clin Invest. 2018;128:3682–91.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Professor En Min Li of Shantou University Medical College, Shantou University, China, for giving us the cell lines (HeLa, EC109, HepG2, EJ, and THLE-3 cells) used in this study.

Code availability

Not applicable

Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81903649, 31372558, and 31872596); China Postdoctoral Science Foundation (grant number 2019M663144); the Medical Research Foundation of Guangdong Province (grant number A2020193); the Natural Science Foundation of Guangdong Province (grant number 2017A030311032 and 2017A030310611); the Department of Education of Guangdong Province (grant number 2017KZDXM033); and Shenzhen Basic Research Project (grant number JCYJ20160429093033251).

Author information

Authors and Affiliations

  1. Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China

    Shangjie Liu, Jude Juventus Aweya, Liyuan Zheng, Zhou Zheng, He Huang, Fan Wang, Defu Yao & Yueling Zhang

  2. Institute of Urology, The Affiliated Shenzhen Luohu Hospital of Shantou University Medical College, Shantou University, Shantou, 515063, China

    Shangjie Liu & Tong Ou

  3. STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou, 515063, China

    Shangjie Liu, Jude Juventus Aweya, Liyuan Zheng, Zhou Zheng, He Huang, Fan Wang, Defu Yao & Yueling Zhang

Authors
  1. Shangjie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jude Juventus Aweya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liyuan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhou Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. He Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Defu Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tong Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yueling Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, Yueling Zhang; formal analysis, Shangjie Liu, Jude Juventus Aweya, Liyuan Zheng, He Huang and Fan Wang; funding acquisition, Shangjie Liu, Yueling Zhang, and Tong Ou; investigation, Shangjie Liu, Jude Juventus Aweya, Liyuan Zheng, Zhou Zheng, He Huang, Fan Wang, and Defu Yao ; resources, Zhou Zheng and Defu Yao; supervision, Yueling Zhang; writing–original draft, Shangjie Liu, Jude Juventus Aweya, and Yueling Zhang; writing–review and editing, Shangjie Liu, Jude Juventus Aweya, and Tong Ou. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Tong Ou or Yueling Zhang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

Not applicable

Consent to participate

Not applicable

Consent for publication

Not applicable

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Graphical Headlights

• Cationic peptide LvHemB1 selectively permeabilizes cancer cells.

• LvHemB1 targets mitochondrial voltage-dependent anion channel 1 (VDAC1).

• Binding of LvHemB1 to VDAC1 causes loss in mitochondrial membrane potential (ΔΨ).

• Loss of ΔΨ increases levels of ROS and apoptotic proteins, which results in apoptosis.

Supplementary Information

Supplementary Materials

: The following are available online at www.mdpi.com/xxx/s1, Table S1: Protein identification by LC-MS/MS. (XLSX 74 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, S., Aweya, J.J., Zheng, L. et al. LvHemB1, a novel cationic antimicrobial peptide derived from the hemocyanin of Litopenaeus vannamei, induces cancer cell death by targeting mitochondrial voltage-dependent anion channel 1. Cell Biol Toxicol 38, 87–110 (2022). https://doi.org/10.1007/s10565-021-09588-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-021-09588-y

Keywords

Search

Navigation