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Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate

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Abstract

The peptide melittin is a promising possibility for cancer treatment. The present research evaluated the anticancer impact in vitro on breast cell lines using melittin, melittin-loaded pectin, and blank pectin. The “thin-layer hydration approach” was employed for generating the pectines; several melittin pectinal formulations were developed and studied in shape, size, polydispersity index, entrapment effectiveness, release kinetics, and stability. Breast cancer cells were tested using the hemolytic ability method, flow cytometry, the MTT test, the soft agar colony method, and wound healing analysis. The gene’s transcription was determined using real-time PCR (P < 0.05). Due to improved targeting, the effectiveness of encapsulation (83.57 ± 1.06), PDI (0.298 ± 0.65), and release percentage, as well as a significant anticancer impact on cell lines, this research demonstrated that melittin-loaded pectin is an adequate replacement in the treatment of breast cancer. The melittin-loaded pectin has a more significant impact on gene transcription in the examined cells than in other samples; it up-regulates the transcription of the Bax, P57, caspase3, and caspase9 genes while down-regulating the transcription of the MMP2, MMP2, and MMP9 genes (P < 0.05). In addition, compared to the melittin samples, they increased the apoptosis rate (by more than 40%) and hindered the invasion and migration of both cell lines. Our research has conclusively shown that melittin plasmid-loaded pectin has more anticancer properties than free melittin. This study has shown that pectins are appropriate vesicle transporters for melittin in contrast to the free form.

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Data Availability

The data generated or analyzed during this study are included in this article and its additional materials.

References

  • Amini E, Baharara J, Nikdel N, Salek Abdollahi F (2015) Cytotoxic and pro-apoptotic effects of honey bee venom and chrysin on human ovarian cancer cells. Asia Pac J Med Toxicol 4(2):68–73

    CAS  Google Scholar 

  • Andersson A, Biverståhl H, Nordin J, Danielsson J, Lindahl E, Mäler L (2007) The membrane-induced structure of melittin is correlated with the fluidity of the lipids. Biochim et Biophys Acta (BBA)-Biomembranes 1768(1):115–121

    Article  CAS  Google Scholar 

  • Azimifar MA, Salmasi Z, Doosti A, Babaei N, Hashemi M (2021) Evaluation of the efficiency of modified PAMAM dendrimer with low molecular weight protamine peptide to deliver IL-12 plasmid into stem cells as cancer therapy vehicles. Biotechnol Prog 37(4):e3175

    CAS  PubMed  Google Scholar 

  • Baranova A, Krasnoselskyi M, Starikov V, Kartashov S, Zhulkevych I, Vlasenko V, Oleshko K, Bilodid O, Sadchikova M, Vinnyk Y (2022) Triple-negative breast cancer: current treatment strategies and factors of negative prognosis. J Med Life 15(2):153

    Article  PubMed  PubMed Central  Google Scholar 

  • Boman HG, Wade D, Boman IA, Wåhlin B, Merrifield RB (1989) Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids. FEBS Lett 259(1):103–106

    Article  CAS  PubMed  Google Scholar 

  • Cao W, Chen HD, Yu YW, Li N, Chen WQ (2021) Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J 134(07):783–791

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng Q, Wei T, Jia Y, Farbiak L, Zhou K, Zhang S, Wei Y, Zhu H, Siegwart DJ (2018) Dendrimer-based lipid nanoparticles deliver therapeutic FAH mRNA to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia type I. Adv Mater 30(52):1805308

    Article  Google Scholar 

  • Choi KE, Hwang CJ, Gu SM, Park MH, Kim JH, Park JH, Ahn YJ, Kim JY, Song MJ, Song HS, Han SB (2014) Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins 6(8):2210–2228

    Article  PubMed  PubMed Central  Google Scholar 

  • Dabbagh Moghaddam F, Akbarzadeh I, Marzbankia E, Farid M, Khaledi L, Reihani AH, Javidfar M, Mortazavi P (2021) Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect. Cancer Nanotechnol 12(1):14

    Article  CAS  Google Scholar 

  • Daniluk K, Kutwin M, Grodzik M, Wierzbicki M, Strojny B, Szczepaniak J, Bałaban J, Sosnowska M, Chwalibog A, Sawosz E, Jaworski S (2019) Use of selected carbon nanoparticles as melittin carriers for MCF-7 and MDA-MB-231 human breast cancer cells. Materials 13(1):90

    Article  PubMed  PubMed Central  Google Scholar 

  • Deuker MF, Mailänder V, Morsbach S, Landfester K (2023) Anti-PEG antibodies enriched in the protein corona of PEGylated nanocarriers impact the cell uptake. Nanoscale Horizons 8(10):1377–1385

    Article  CAS  PubMed  Google Scholar 

  • Dhilip Kumar SS, Abrahamse H (2022) Recent advances in the development of biocompatible nanocarriers and their cancer cell targeting efficiency in photodynamic therapy. Front Chem 10:969809

    Article  PubMed  PubMed Central  Google Scholar 

  • Diwan D, Cheng L, Usmani Z, Sharma M, Holden N, Willoughby N, Sangwan N, Baadhe RR, Liu C, Gupta VK Microbial cancer therapeutics: A promising approach. InSeminars in Cancer Biology 2022 Nov 1 (Vol. 86, pp. 931–950). Academic Press

  • Fasano C, Grossi V, Forte G, Simone C (2022) Short Linear motifs in Colorectal Cancer Interactome and Tumorigenesis. Cells 11(23):3739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng JP, Zhu R, Jiang F, Xie J, Gao C, Li M, Jin H, Fu D (2020) Melittin-encapsulating peptide hydrogels for enhanced delivery of impermeable anticancer peptides. Biomaterials Sci 8(16):4559–4569

    Article  CAS  Google Scholar 

  • Garcia-Bereguiain MA, Samhan-Arias AK, Martin-Romero FJ, Gutierrez-Merino C (2008) Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2 + channels. Antioxid Redox Signal 10(1):31–42

    Article  CAS  PubMed  Google Scholar 

  • Ghulam A, Ali F, Sikander R, Ahmad A, Ahmed A, Patil S (2022) ACP-2DCNN: deep learning-based model for improving prediction of anticancer peptides using two-dimensional convolutional neural network. Chemometr Intell Lab Syst 226:104589

    Article  CAS  Google Scholar 

  • Giribaldi J, Smith JJ, Schroeder CI (2021) Recent developments in animal venom peptide nanotherapeutics with improved selectivity for cancer cells. Biotechnol Adv 50:107769

    Article  CAS  PubMed  Google Scholar 

  • Han YP, Lin HW, Li H (2023) Cancer Stem cells in Tumours of the Central Nervous System in children: a Comprehensive Review. Cancers 15(12):3154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Huang J, Chen Y (2010) Alpha-helical cationic antimicrobial peptides: relationships of structure and function. Protein Cell 1:143–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islam N, Miyazaki K (2009) Nanotechnology innovation system: understanding hidden dynamics of nanoscience fusion trajectories. Technol Forecast Soc Change 76(1):128–140

    Article  Google Scholar 

  • Khalil SR, Abd-Elhakim YM, Selim ME, Al-Ayadhi LY (2015) Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: the expression pattern of Bcl-2 and Caspase-3 apoptotic genes. Neurotoxicology 49:121–131

    Article  CAS  PubMed  Google Scholar 

  • Kumar SD, Park JH, Kim HS, Seo CD, Ajish C, Kim EY, Lim HS, Shin SY (2022) Cationic, amphipathic small molecules based on a triazine-piperazine-triazine scaffold as a new class of antimicrobial agents. Eur J Med Chem 243:114747

    Article  Google Scholar 

  • Liu Y, Li S, Ding C, Ge Z, Aierken A, Li J, Qin L, Liu J, Guo X, Wang Y, Xing Z (2023) Dual-responsive and controlled-release paclitaxel-loaded mesoporous silicon nanoparticles with cell membrane coating for homologous targeted therapy of tongue squamous cell carcinoma. Mater Design 229:111886

    Article  CAS  Google Scholar 

  • Lv S, Sylvestre M, Song K, Pun SH (2021) Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials 277:121076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majidinia M, Mirza-Aghazadeh‐Attari M, Rahimi M, Mihanfar A, Karimian A, Safa A, Yousefi B (2020) Overcoming multidrug resistance in cancer: recent progress in nanotechnology and new horizons. IUBMB Life 72(5):855–871

    Article  CAS  PubMed  Google Scholar 

  • Meuten DJ (2002) Diagnostic schemes and algorithms. Tum Domes Anim. https://doi.org/10.1002/9781119181200

    Article  Google Scholar 

  • Moezi P, Kargar M, Doosti A, Khoshneviszadeh M (2019) Multiplex touchdown PCR assay to enhance specificity and sensitivity for concurrent detection of four foodborne pathogens in raw milk. J Appl Microbiol 127(1):262–273

    Article  CAS  PubMed  Google Scholar 

  • Moghaddam FD, Mortazavi P, Hamedi S, Nabiuni M, Roodbari NH (2020) Apoptotic effects of melittin on 4T1 breast cancer cell line is associated with up regulation of Mfn1 and Drp1 mRNA expression. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). Appl Biochem Biotechnol 20(7):790–799

    CAS  Google Scholar 

  • Mokhtar N, Fouda F, Zaazaa AM, Mahmoud MH (2022) Nano-encapsulation of doxorubicin using pectin: Safety an activity on chemotherapy-induced cardiotoxicity in carcinoma mice. Lett Appl NanoBio Sci 12(4):107

    Article  Google Scholar 

  • Nguyen TT, Postlewait LM, Zhang C, Meisel JL, O’Regan R, Badve S, Kalinsky K, Li X (2022) Utility of Oncotype DX score in clinical management for T1 estrogen receptor positive, HER2 negative, and lymph node negative breast cancer. Breast Cancer Res Treat 192(3):509–516

    Article  CAS  PubMed  Google Scholar 

  • Nim B, Rahayu SS, Thananukul K, Eang C, Opaprakasit M, Petchsuk A, Kaewsaneha C, Polpanich D, Opaprakasit P (2023) Sizing down and functionalizing polylactide (PLA) resin for synthesis of PLA-based polyurethanes for use in biomedical applications. Sci Rep 13(1):2284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pandey P, Khan F, Khan MA, Kumar R, Upadhyay TK (2023) An updated review summarizing the Anticancer efficacy of Melittin from Bee Venom in several models of human cancers. Nutrients 15(14):3111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park KS, Svennerholm K, Crescitelli R, Lässer C, Gribonika I, Lötvall J (2021) Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy. J Extracell Vesicles 10(9):e12120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paray BA, Ahmad A, Khan JM, Taufiq F, Pathan A, Malik A, Ahmed MZ (2021) The role of the multifunctional antimicrobial peptide melittin in gene delivery. Drug Discovery Today 26(4):1053–1059

    Article  CAS  PubMed  Google Scholar 

  • Piri-Gharaghie T (2021) Polycystic ovary syndrome and genetic factors influencing its development: a review article. Personalized Med J 6(23):25–29

    Google Scholar 

  • Piri Gharaghie T, Doosti A, Mirzaei SA (2021) Prevalence and antibiotic resistance pattern of Acinetobacter spp. infections in Shahrekord medical centers. Dev Biol 13(4):35–46

    Google Scholar 

  • Rahman M, Ahmad MZ, Kazmi I, Akhter S, Afzal M, Gupta G, Ahmed FJ, Anwar F (2012) Advancement in multifunctional nanoparticles for the effective treatment of cancer. Expert Opin Drug Deliv 9(4):367–381

    Article  CAS  PubMed  Google Scholar 

  • Rai A, Ferrão R, Palma P, Patricio T, Parreira P, Anes E, Tonda-Turo C, Martins MC, Alves N, Ferreira L (2022) Antimicrobial peptide-based materials: opportunities and challenges. J Mater Chem B 10(14):2384–2429

    Article  CAS  PubMed  Google Scholar 

  • Raj R, Kumar A, Sood P, Kumar R, Rana V, Randomized Phase III (2023) Trial Comparing Epirubicin/Doxorubicin plus Docetaxel and Epirubicin/Doxorubicin plus paclitaxel as First Line treatment in women with advanced breast Cancer. J Res Appl Sci Biotechnol 2(3):55–63

    Article  Google Scholar 

  • Rosales TK, Fabi JP (2022) Pectin-based nanoencapsulation strategy to improve the bioavailability of bioactive compounds. Int J Biol Macromol 229:11–21

    Article  PubMed  Google Scholar 

  • Ryu JS, Jang BH, Jo YS, Kim SJ, Eom TI, Kim MC, Ko HJ, Sim SS (2014) The effect of acteoside on intracellular ca 2 + mobilization and phospholipase C activity in RBL-2H3 cells stimulated by melittin. Arch Pharm Res 37:239–244

    Article  CAS  PubMed  Google Scholar 

  • Sharma K, Singh V, Arora A (2011) Natural biodegradable polymers as matrices in transdermal drug delivery. Int J Drug Dev Res 3(2):85–103

    Google Scholar 

  • Singh AK, Malviya R, Prajapati B, Singh S, Yadav D, Kumar A (2023) Nanotechnology-aided Advancement in combating the Cancer Metastasis. Pharmaceuticals 16(6):899

    Article  PubMed  PubMed Central  Google Scholar 

  • Song K, Hao Y, Liu Y, Cao R, Zhang X, He S, Wen J, Zheng W, Wang L, Zhang Y (2023) Preparation of pectin-chitosan hydrogels based on bioadhesive-design micelle to prompt bacterial infection wound healing. Carbohydr Polym 300:120272

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Wei Z, Xue C (2023) Preparation and characterization of multifunctional films based on pectin and carboxymethyl chitosan: forming microchambers for high-moisture fruit preservation. Food Packaging Shelf Life 37:101073

    Article  CAS  Google Scholar 

  • Toulouie S, Johanning G, Shi Y (2021) Chimeric antigen receptor T-cell immunotherapy in breast cancer: development and challenges. J Cancer 12(4):1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan L, Zhang D, Zhang J, Ren L (2018) TT-1, an analog of melittin, triggers apoptosis in human thyroid cancer TT cells via regulating caspase, Bcl-2 and Bax. Oncol Lett 15(1):1271–1278

    PubMed  Google Scholar 

  • Wang N, Cheng X, Li N, Wang H, Chen H (2019) Nanocarriers and their loading strategies. Adv Healthc Mater 8(6):1801002

    Article  Google Scholar 

  • Yao X, Bunt C, Liu M, Quek SY, Shaw J, Cornish J, Wen J (2023) Enhanced Cellular Uptake and Transport of Bovine lactoferrin using pectin-and Chitosan-modified solid lipid nanoparticles. Pharmaceutics 15(8):2168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yap KM, Sekar M, Fuloria S, Wu YS, Gan SH, Mat Rani NN, Subramaniyan V, Kokare C, Lum PT, Begum MY, Mani S (2021) Drug delivery of natural products through nanocarriers for effective breast cancer therapy: A comprehensive review of literature. Int J Nanomed 16:7891–7941

    Article  CAS  Google Scholar 

  • Yu-Wei D, Li ZS, Xiong SM, Huang G, Luo YF, Huo TY, Zhou MH, Zheng YW (2020) Paclitaxel induces apoptosis through the TAK1–JNK activation pathway. FEBS Open Bio 10(8):1655–1667

    Article  PubMed  PubMed Central  Google Scholar 

  • Zafra-Tanaka JH, Tenorio-Mucha J, Villarreal-Zegarra D, Carrillo-Larco R, Bernabe-Ortiz A (2020) Cancer-related mortality in Peru: Trends from 2003 to 2016. PLoS ONE 15(2):e0228867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang HQ, Sun C, Xu N, Liu W (2024) The current landscape of the antimicrobial peptide melittin and its therapeutic potential. Front Immunol 15

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Authors and Affiliations

  1. Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Esmaeil Alibeigi, Arsham Azari Dehkordi, Milad Asadian, Abbas Doosti & Tohid Piri-Gharaghie

  2. Biotechnology Research Center, Faculty of Biological Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran

    Tohid Piri-Gharaghie

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  1. Esmaeil Alibeigi
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  2. Arsham Azari Dehkordi
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  3. Milad Asadian
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  4. Abbas Doosti
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  5. Tohid Piri-Gharaghie
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Contributions

I‑AB designed and performed experiments reported in the paper, analyzed data and wrote the manuscript; T‑PG helped with experiments, data analysis, and contributed to manuscript editing; A‑D and M‑A help the internalization experiments, data analysis for internalization; A‑AD and A‑D provided the information of leukemia clinical treatments and current challenges.

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Correspondence to Abbas Doosti.

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Alibeigi, E., Dehkordi, A.A., Asadian, M. et al. Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate. Int J Pept Res Ther 30, 17 (2024). https://doi.org/10.1007/s10989-024-10593-y

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