Combined Protein and Alkaloid Research of Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Nov 13

PMID 34769268

Citations 6

Authors

Robert Nawrot

Alicja Warowicka

Piotr Jozef Rudzki

Oskar Musidlak

Katarzyna Magdalena Dolata

Jacek Musijowski

Elzbieta Urszula Stolarczyk

Anna Gozdzicka-Jozefiak

Affiliations

Soon will be listed here.

Abstract

L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction. We describe the isolation and identification of a novel major latex protein (CmMLP1) composed of 147 amino acids and present a model of its structure containing a conserved hydrophobic cavity with high affinity to berberine, 8-hydroxycheleritrine, and dihydroberberine. CmMLP1 and the accompanying three alkaloids were present in the eluted chromatographic fractions of latex. They decreased in vitro viability of human cervical cancer cells (HPV-negative and HPV-positive). We combined, for the first time, research on macromolecular and low-molecular-weight compounds of latex-bearing plants in contrast to other studies that investigated proteins and alkaloids separately. The observed interaction between latex protein and alkaloids may influence our knowledge on plant defense. The proposed toolbox may help in further understanding of plant disease resistance and in pharmacological research.

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The Activity of L. Latex and Its Components on HPV Reveal Insights into the Antiviral Molecular Mechanism.

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References

Eid S, El-Readi M, Wink M . Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells. Phytomedicine. 2012; 19(14):1288-97. DOI: 10.1016/j.phymed.2012.08.010. View

Fujita K, Inui H . Review: Biological functions of major latex-like proteins in plants. Plant Sci. 2021; 306:110856. DOI: 10.1016/j.plantsci.2021.110856. View

Marchler-Bauer A, Anderson J, Chitsaz F, Derbyshire M, DeWeese-Scott C, Fong J . CDD: specific functional annotation with the Conserved Domain Database. Nucleic Acids Res. 2008; 37(Database issue):D205-10. PMC: 2686570. DOI: 10.1093/nar/gkn845. View

Goodwin E, DiMaio D . Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc Natl Acad Sci U S A. 2000; 97(23):12513-8. PMC: 18795. DOI: 10.1073/pnas.97.23.12513. View

Nawrot R, Lippmann R, Matros A, Musidlak O, Nowicki G, Mock H . Proteomic comparison of Chelidonium majus L. latex in different phases of plant development. Plant Physiol Biochem. 2017; 112:312-325. DOI: 10.1016/j.plaphy.2017.01.010. View

Warowicka A, Popenda L, Bartkowiak G, Musidlak O, Litowczenko-Cybulska J, Kuzma D . Protoberberine compounds extracted from Chelidonium majus L. as novel natural photosensitizers for cancer therapy. Phytomedicine. 2019; 64:152919. DOI: 10.1016/j.phymed.2019.152919. View

Nawrot R, Barylski J, Lippmann R, Altschmied L, Mock H . Combination of transcriptomic and proteomic approaches helps to unravel the protein composition of Chelidonium majus L. milky sap. Planta. 2016; 244(5):1055-1064. PMC: 5052312. DOI: 10.1007/s00425-016-2566-7. View

Xiao C, Fu B, Li Z, Mushtaq G, Kamal M, Li J . Observations on the expression of human papillomavirus major capsid protein in HeLa cells. Cancer Cell Int. 2015; 15:53. PMC: 4461987. DOI: 10.1186/s12935-015-0206-0. View

Park C, Kim K, Shin R, Park J, Shin Y, Paek K . Pathogenesis-related protein 10 isolated from hot pepper functions as a ribonuclease in an antiviral pathway. Plant J. 2003; 37(2):186-98. DOI: 10.1046/j.1365-313x.2003.01951.x. View

10.

Nessler C . Sequence analysis of two new members of the major latex protein gene family supports the triploid-hybrid origin of the opium poppy. Gene. 1994; 139(2):207-9. DOI: 10.1016/0378-1119(94)90756-0. View

11.

Chruszcz M, Ciardiello M, Osinski T, Majorek K, Giangrieco I, Font J . Structural and bioinformatic analysis of the kiwifruit allergen Act d 11, a member of the family of ripening-related proteins. Mol Immunol. 2013; 56(4):794-803. PMC: 3783527. DOI: 10.1016/j.molimm.2013.07.004. View

12.

Nawrot J, Wilk-Jedrusik M, Nawrot S, Nawrot K, Wilk B, Dawid-Pac R . Milky Sap of Greater Celandine ( L.) and Anti-Viral Properties. Int J Environ Res Public Health. 2020; 17(5). PMC: 7084376. DOI: 10.3390/ijerph17051540. View

13.

Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I . Human papillomavirus molecular biology and disease association. Rev Med Virol. 2015; 25 Suppl 1:2-23. PMC: 5024016. DOI: 10.1002/rmv.1822. View

14.

Nawrot R . Defense-related Proteins from Chelidonium majus L. as Important Components of its Latex. Curr Protein Pept Sci. 2017; 18(8):864-880. DOI: 10.2174/1389203718666170406124013. View

15.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

16.

Zielinska S, Jezierska-Domaradzka A, Wojciak-Kosior M, Sowa I, Junka A, Matkowski A . Greater Celandine's Ups and Downs-21 Centuries of Medicinal Uses of From the Viewpoint of Today's Pharmacology. Front Pharmacol. 2018; 9:299. PMC: 5912214. DOI: 10.3389/fphar.2018.00299. View

17.

Yang C, Liang S, Wang H, Han L, Wang F, Cheng H . Cotton major latex protein 28 functions as a positive regulator of the ethylene responsive factor 6 in defense against Verticillium dahliae. Mol Plant. 2015; 8(3):399-411. DOI: 10.1016/j.molp.2014.11.023. View

18.

Teixidor-Toneu I, Jordan F, Hawkins J . Comparative phylogenetic methods and the cultural evolution of medicinal plant use. Nat Plants. 2018; 4(10):754-761. DOI: 10.1038/s41477-018-0226-6. View

19.

Malter D, Wolf S . Melon phloem-sap proteome: developmental control and response to viral infection. Protoplasma. 2010; 248(1):217-24. DOI: 10.1007/s00709-010-0215-8. View

20.

Wallner B, Elofsson A . Can correct protein models be identified?. Protein Sci. 2003; 12(5):1073-86. PMC: 2323877. DOI: 10.1110/ps.0236803. View