Effect of IFN‑γ encapsulated liposomes on major signal transduction pathways in the lymphocytes of patients with lung cancer

Alhawamdeh,Maysa; Almajali,Belal; Hourani,Wafa; Al‑Jamal,Hamid Ali Nagi; Al‑Wajeeh,Abdullah Saleh; Mwafi,Nesrin Riad; Al‑Hajaya,Yousef; Saad,Hanan Kamel M.; Anderson,Diana; Odeh,Mahmoud; Tarawneh,Ibraheam A.

doi:10.3892/ol.2023.14141

Effect of IFN‑γ encapsulated liposomes on major signal transduction pathways in the lymphocytes of patients with lung cancer

Authors:
- Maysa Alhawamdeh
- Belal Almajali
- Wafa Hourani
- Hamid Ali Nagi Al‑Jamal
- Abdullah Saleh Al‑Wajeeh
- Nesrin Riad Mwafi
- Yousef Al‑Hajaya
- Hanan Kamel M. Saad
- Diana Anderson
- Mahmoud Odeh
- Ibraheam A. Tarawneh
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Affiliations: Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Mutah University, Al‑Karak 61710, Jordan, Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Al‑Ahliyya Amman University, Amman 19111, Jordan, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan, School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Nerus, Terengganu 21300, Malaysia, Metabolomics Department, Anti‑Doping Lab Qatar, Doha 27775, Qatar, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Mutah University, Al‑Karak 61710, Jordan, Division of Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, UK, Business Faculty, Zarqa University, Zarqa 13110, Jordan, School of Graduate Studies, Management and Science University, Shah Alam, Selangor 40100, Malaysia
Published online on: November 8, 2023 https://doi.org/10.3892/ol.2023.14141
Article Number: 8
Copyright: © Alhawamdeh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Globally, lung cancer affected 2.2 million individuals and caused 1.8 million deaths in 2021. Lung cancer is caused by smoking, genetics and other factors. IFN‑γ has anticancer activity. However, the mechanism by which IFN‑γ has an effect on lung cancer is not fully understood. The present study aimed to assess the effect of IFN‑γ on the peripheral lymphocytes of patients with lung cancer compared with healthy controls. The efficacy of IFN‑γ against oxidative stress was assessed using a comet repair assay and the effects of IFN‑γ on p53, PARP1 and OGG1 genes and protein levels in lymphocytes was evaluated by RT‑qPCR and western blotting. DNA damage was significantly reduced in the lymphocytes of patients treated with IFN‑γ. However, there was no effect in the cells of healthy individuals after treatment with naked IFN‑γ [IFN‑γ (N)] and liposomal IFN‑γ [IFN‑γ (L)]. Following treatment with IFN‑γ (N) and IFN‑γ (L), the p53, PARP1 and OGG1 protein and gene expression levels were significantly increased (P<0.001). It has been suggested that IFN‑γ may induce p53‑mediated cell cycle arrest and DNA repair in patients. These findings supported the idea that IFN‑γ (N) and IFN‑γ (L) may serve a significant role in the treatment of lung cancer, via cell cycle arrest of cancer cells and repair mechanisms.

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1	Oo AM, Mohd Adnan LH, Nor NM, Simbak N, Ahmad NZ and Lwin OM: Immunomodulatory effects of flavonoids: An experimental study on natural-killer-cell-mediated cytotoxicity against lung cancer and cytotoxic granule secretion profile. Proceedings Singapore Healthcare. 30:279–285. 2020. View Article : Google Scholar
2	Daud NNNNM, Septama AW, Simbak N, Bakar NHA and Rahmi EP: Synergistic effect of flavonoids from artocarpus heterophyllus heartwoods on anticancer activity of cisplatin against H460 and MCF-7 cell lines. Nat Product Sci. 25:311–316. 2019. View Article : Google Scholar
3	Miller CH, Maher SG and Young HA: Clinical use of interferon-γ. Ann N Y Acad Sci. 1182:69–79. 2009. View Article : Google Scholar : PubMed/NCBI
4	Ferreira VL, Borba HHL, Bonetti AdF, Leonart LP and Pontarolo R: Cytokines and interferons: Types and functions. Autoantibodies Cytokines. 13:2018.
5	Castro F, Cardoso AP, Gonçalves RM, Serre K and Oliveira MJ: Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol. 9:8472018. View Article : Google Scholar : PubMed/NCBI
6	Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K and Igarashi S: Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 10:511–518. 2006. View Article : Google Scholar : PubMed/NCBI
7	Li Y, Bao Q, Yang S, Yang M and Mao C: Bionanoparticles in cancer imaging, diagnosis, and treatment. View. 3:202000272022. View Article : Google Scholar
8	de Ruiter MV, Klem R, Luque D, Cornelissen JJ and Castón JR: Structural nanotechnology: Three-dimensional cryo-EM and its use in the development of nanoplatforms for in vitro catalysis. Nanoscale. 11:4130–4146. 2019. View Article : Google Scholar : PubMed/NCBI
9	Yang Z and Chen H: The recent progress of inorganic-based intelligent responsive nanoplatform for tumor theranostics. View. 3:202200092022. View Article : Google Scholar
10	Koizumi S-i, Wakita D, Sato T, Mitamura R, Izumo T, Shibata H, Kiso Y, Chamoto K, Togashi Y, Kitamura H and Nishimura T: Essential role of Toll-like receptors for dendritic cell and NK1. 1+ cell-dependent activation of type 1 immunity by Lactobacillus pentosus strain S-PT84. Immunol Lett. 120:14–19. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ramos TI, Villacis-Aguirre CA, Santiago Vispo N, Santiago Padilla L, Pedroso Santana S, Parra NC and Alonso JRT: Forms and methods for interferon's encapsulation. Pharmaceutics. 13:15332021. View Article : Google Scholar : PubMed/NCBI
12	Jailani MTM, Totten J, Nevin J and Halbert G: ID 180. Fabrication, characterisation and in vitro study of dual-loaded irinotecan/cisplatin liposomes. J Pharmacy Bioallied Sci. 12:2020.
13	Hirai M, Kimura R, Takeuchi K, Hagiwara Y, Kawai-Hirai R, Ohta N, Igarashi N and Shimuzu N: Structure of liposome encapsulating proteins characterized by X-ray scattering and shell-modeling. J Synchrotron Radiat. 20:869–874. 2013. View Article : Google Scholar : PubMed/NCBI
14	Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y and Li Y: Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct Target Ther. 6:2632021. View Article : Google Scholar : PubMed/NCBI
15	Kalm M, Andreasson U, Björk-Eriksson T, Zetterberg H, Pekny M, Blennow K, Pekna M and Blomgren K: C3 deficiency ameliorates the negative effects of irradiation of the young brain on hippocampal development and learning. Oncotarget. 7:193822016. View Article : Google Scholar : PubMed/NCBI
16	Wirth M, Plattner V and Gabor F: Strategies to improve drug delivery in bladder cancer therapy. Expert Opin Drug Deliv. 6:727–744. 2009. View Article : Google Scholar : PubMed/NCBI
17	Pisal DS, Kosloski MP and Balu-Iyer SV: Delivery of therapeutic proteins. J Pharm Sci. 99:2557–2575. 2010. View Article : Google Scholar : PubMed/NCBI
18	Yu H, Gao HY, Guo H, Wang GZ, Yang YQ, Hu Q, Liang LJ, Zhao Q, Xie DW, Rao Y and Zhou GB: Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells. Acta Pharmacol Sinica. 43:692–702. 2022. View Article : Google Scholar : PubMed/NCBI
19	Almajali B, Johan MF, Al-Wajeeh AS, Wan Taib WR, Ismail I, Alhawamdeh M, Al-Tawarah NM, Ibrahim WN, Al-Rawashde FA and Al-Jamal HAN: Gene expression profiling and protein analysis reveal suppression of the C-Myc oncogene and inhibition JAK/STAT and PI3K/AKT/mTOR signaling by thymoquinone in acute myeloid leukemia cells. Pharmaceuticals. 15:3072022. View Article : Google Scholar : PubMed/NCBI
20	Williams AB and Schumacher B: p53 in the DNA-damage-repair process. Cold Spring Harb Perspect Med. 6:a0260702016. View Article : Google Scholar : PubMed/NCBI
21	Xu X, Jin S, Ma Y, Fan Z, Yan Z, Li W, Song Q, You W, Lyu Z, Song Y, et al: miR-30a-5p enhances paclitaxel sensitivity in non-small cell lung cancer through targeting BCL-2 expression. J Mol Med (Berl). 95:861–871. 2017. View Article : Google Scholar : PubMed/NCBI
22	Slupphaug G, Kavli B and Krokan HE: The interacting pathways for prevention and repair of oxidative DNA damage. Mutat Res. 531:231–251. 2003. View Article : Google Scholar : PubMed/NCBI
23	Noren Hooten N, Kompaniez K, Barnes J, Lohani A and Evans MK: Poly(ADP-ribose) polymerase 1 (PARP-1) binds to 8-oxoguanine-DNA glycosylase (OGG1). J Biol Chem. 286:44679–44690. 2011. View Article : Google Scholar : PubMed/NCBI
24	Alhawamdeh M, Isreb M, Aziz A, Jacob BK, Anderson D and Najafzadeh M: Interferon-γ liposome: A new system to improve drug delivery in the treatment of lung cancer. ERJ Open Res. 7:00555–2020. 2021. View Article : Google Scholar : PubMed/NCBI
25	Van Slooten M, Boerman O, Romøren K, Kedar E, Crommelin D and Storm G: Liposomes as sustained release system for human interferon-γ: Biopharmaceutical aspects. Biochim Biophys Acta. 1530:134–145. 2001. View Article : Google Scholar : PubMed/NCBI
26	Haggag YA, Matchett KB, Falconer RA, Isreb M, Jones J, Faheem A, McCarron P and El-Tanani M: Novel ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo. Cancers. 11:2222019. View Article : Google Scholar : PubMed/NCBI
27	Fouad YA and Aanei C: Revisiting the hallmarks of cancer. Am J Cancer Res. 7:10162017.PubMed/NCBI
28	Collins AR: The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 26:249–261. 2004. View Article : Google Scholar : PubMed/NCBI
29	Alhawamdeh MF: Applying a new technique, the interferon gamma liposomal delivery system to improve drug delivery in the treatment of lung cancer. University of Bradford; 2021, PubMed/NCBI
30	Rivlin N, Brosh R, Oren M and Rotter V: Mutations in the p53 tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer. 2:466–474. 2011. View Article : Google Scholar : PubMed/NCBI
31	Yin T, Wang P, Li J, Wang Y, Zheng B, Zheng R, Cheng D and Shuai X: Tumor-penetrating codelivery of siRNA and paclitaxel with ultrasound-responsive nanobubbles hetero-assembled from polymeric micelles and liposomes. Biomaterials. 35:5932–5943. 2014. View Article : Google Scholar : PubMed/NCBI
32	Lieschke E, Wang Z, Kelly GL and Strasser A: Discussion of some ‘knowns’ and some ‘unknowns’ about the tumour suppressor p53. J Mol Cell Biol. 11:212–223. 2019. View Article : Google Scholar : PubMed/NCBI
33	Chatterjee N and Walker GC: Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen. 58:235–263. 2017. View Article : Google Scholar : PubMed/NCBI
34	Fukui T, Matsui K, Kato H, Takao H, Sugiyama Y, Kunieda K and Saji S: Significance of apoptosis induced by tumor necrosis factor-α and/or interferon-γ against human gastric cancer cell lines and the role of the p53 gene. Surg Today. 33:847–853. 2003. View Article : Google Scholar : PubMed/NCBI
35	Thiem A, Hesbacher S, Kneitz H, di Primio T, Heppt MV, Hermanns HM, Goebeler M, Meierjohann S, Houben R and Schrama D: IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression. J Exp Clin Cancer Res. 38:3972019. View Article : Google Scholar : PubMed/NCBI
36	Midgley CA and Lane DP: p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 15:1179–1189. 1997. View Article : Google Scholar : PubMed/NCBI
37	Zhang M, Zhang Y, Xu E, Mohibi S, de Anda DM, Jiang Y, Zhang J and Chen X: Rbm24, a target of p53, is necessary for proper expression of p53 and heart development. Cell Death Differ. 25:1118–1130. 2018. View Article : Google Scholar : PubMed/NCBI