Abstract
Objective
Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine.
Results
Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential.
Conclusions
Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ajalla Aleixo MA, Rangel VL, Rustiguel JK, de Padua RAP, Nonato MC (2019) Structural, biochemical and biophysical characterization of recombinant human fumarate hydratase. FEBS J 286:1925–1940. https://doi.org/10.1111/febs.14782
El Arfani C, De Veirman K, Maes K, De Bruyne E, Menu E (2018) Metabolic features of multiple myeloma. Int J Mol Sci 19:1200. https://doi.org/10.3390/ijms19041200
Kozjak-Pavlovic V (2017) The MICOS complex of human mitochondria. Cell Tissue Res 367:83–93. https://doi.org/10.1007/s00441-016-2433-7
Krasnov GS, Dmitriev AA, Lakunina VA, Kirpiy AA, Kudryavtseva AV (2013) Targeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy. Expert Opin Ther Targets 17:1221–1233. https://doi.org/10.1517/14728222.2013.833607
Liu J, Hu JL, Shi BW, He Y, Hu WX (2010) Up-regulation of p21 and TNF-alpha is mediated in lycorine-induced death of HL-60 cells. Cancer Cell Int 10:25. https://doi.org/10.1186/1475-2867-10-25
Lozano R et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128. https://doi.org/10.1016/s0140-6736(12)61728-0
Nakano A et al (2012) Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate. J Bioenerg Biomembr 44:31–38. https://doi.org/10.1007/s10863-012-9412-9
Niedzwiecka K et al (2016) Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma. Oncotarget 7:65614–65626. https://doi.org/10.18632/oncotarget.11592
Nonn L, Berggren M, Powis G (2003) Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis. Mol Cancer Res 1:682–689
Rostovtseva TK, Antonsson B, Suzuki M, Youle RJ, Colombini M, Bezrukov SM (2004) Bid, but not Bax, regulates VDAC channels. J Biol Chem 279:13575–13583. https://doi.org/10.1074/jbc.M310593200
Rostovtseva TK, Tan WZ, Colombini M (2005) On the role of VDAC in apoptosis: fact and fiction. J Bioenerg Biomembr 37:129–142. https://doi.org/10.1007/s10863-005-6566-8
Roy M et al (2016) Lycorine downregulates HMGB1 to inhibit autophagy and enhances bortezomib activity in multiple myeloma. Theranostics 6:2209–2224. https://doi.org/10.7150/thno.15584
Roy M, Liang L, Xiao X, Feng P, Ye M, Liu J (2018) Lycorine: a prospective natural lead for anticancer drug discovery. Biomed Pharmacother 107:615–624. https://doi.org/10.1016/j.biopha.2018.07.147
Stark R et al (2014) A role for mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) in the regulation of hepatic gluconeogenesis. J Biol Chem 289:7257–7263. https://doi.org/10.1074/jbc.C113.544759
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (Nos. 81970195, 81600184) and the Fundamental Research Funds for the Central Universities of Central South University (No. 2020zzts425).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yi, H., Shen, X., Wang, H. et al. Protein mass spectrometry reveals lycorine exerting anti-multiple-myeloma effect by acting on VDAC2 and causing mitochondrial abnormalities. Biotechnol Lett 43, 537–546 (2021). https://doi.org/10.1007/s10529-020-03053-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-020-03053-2