Mulberrofuran G inhibits proliferation and migration by inactivating JAK2/STAT3 signaling in lung cancer cells

Authors

  • Hai-Yuan-Bo Guo Department of Medical Oncology, Pinghu Second People’s Hospital, Pinghu City, Zhejiang Province 314200, China.
  • Xiao-Xiao Liu Department of Medical Oncology, Xinchang People's Hospital of Zhejiang Province, Shaoxing City, Zhejiang Province 312500, China.
  • Xiao-Yong Zhu Department of Second Ward of Medical Oncology, Zhuji People's Hospital of Zhejiang Province, Shaoxing City, Zhejiang Province 311800, China. https://orcid.org/0000-0003-0611-7560
  • Zhe Yu Department of Respiratory Medicine, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo City, Zhejiang Province 315099, China. https://orcid.org/0000-0001-5549-4253

DOI:

https://doi.org/10.3329/bjp.v16i4.55198

Keywords:

Mulberrofuran G, lung adenocarcinoma cells, lung squamous cell carcinoma cells, proliferation, migration, JAK2/STAT3 signaling

Abstract

The present study has investigated how mulberrofuran G affects prolifera-tion, invasion, and migration of the lung adenocarcinoma and squamous cell carcinoma. Four different concentrations of mulberrofuran G (1, 5, 10, and 100 μmol/L) were used to simulate human lung adenocarcinoma cells (A549 cells) and squamous-cell carcinoma (NCI-H226 cells). The results showed that mulberrofuran G significantly inhibited the proliferation, invasion, and migration of both A549 and NCI-H226 cells, with a dose-effect relationship. The IC50 inhibited the growth of A549 cells and NCI-H226 cells by mulberrofuran G were 22.5 and 30.6 μmol/L, respectively. It strengthened the expression of CDK4 and MMP9 but significantly weakened the expression of p27 in both A549 cells and NCI-H226 cells. Furthermore, the expression of p-JAK2 and p-STAT3 was significantly down-regulated in drug treatments. In conclusion, mulberrofuran G could inhibit proliferation, migration, and invasion of lung cancer cells via inactivating JAK2/STAT3 signaling.

Downloads

Download data is not yet available.
Abstract
36
Download
19

References

Aaronson DS, Horvath CM. A road map for those who don't know JAK-STAT. Science 2002; 296: 1653-55.

Bartek J, Bartkova J, Lukas J. The retinoblastoma protein pathway and the restriction point. Curr Opin Cell Biol. 1996; 8: 805-14.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424.

Cerfolio RJ, Ghanim AF, Dylewski M, Veronesi G, Spaggiari L, Park BJ. The long-term survival of robotic lobectomy for non–small cell lung cancer: A multi-institutional study. J Thorac Cardiovasc Surg. 2018; 155: 778-86.

Chen Y, Tang J, Lu T, Liu F. CAPN1 promotes malignant behavior and erlotinib resistance mediated by phosphorylation of c-Met and PIK3R2 via degrading PTPN1 in lung adenocarcinoma. Thorac Cancer. 2020; 11: 1848-60.

Chen XL. Lycorine inhibits MDA-MB-231 breast cancer cells proliferation, migration and invasion is associated with Wnt/β-catenin signaling. Bangladesh J Pharmacol. 2018; 13: 192-95.

Colleoni B, Paternot S, Pita JM, Bisteau X, Coulonval K, Davis RJ, Raspé E, Roger PP. JNKs function as CDK4-activating kinases by phosphorylating CDK4 and p21. Oncogene 2017; 36: 4349.

Colomiere M, Ward A, Riley C, Trenerry M, Cameron-Smith D, Findlay J, Ackland L, Ahmed N. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial–mesenchymal transition in ovarian carcinomas. Br J Cancer. 2009; 100: 134.

Driessen EJ, Schulkes KJ, Dingemans A-MC, van Loon JG, Hamaker ME, Aarts MJ, Janssen-Heijnen ML. Patterns of treatment and survival among older patients with stage III non-small cell lung cancer. Lung Cancer. 2018; 116: 55-61.

Fortschegger K, Husa AM, Schinnerl D, Nebral K, Strehl S. Expression of RUNX1-JAK2 in human induced pluripotent stem cell-derived hematopoietic cells activates the JAK-STAT and MYC pathways. Int J Mol Sci. 2021; 22: 7576.

Gupta GP, Massagué J. Cancer metastasis: Building a framework. Cell 2006; 127: 679-95.

Haque I, Ghosh A, Acup S, Banerjee S, Dhar K, Ray A, Sarkar S, Kambhampati S, Banerjee SK. Leptin-induced ER-α-positive breast cancer cell viability and migration is mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway. BMC Cancer. 2018; 18: 99.

Heist RS, Guarino MJ, Masters G, Purcell WT, Starodub AN, Horn L, Scheff RJ, Bardia A, Messersmith WA, Berlin J. Therapy of advanced non–small-cell lung cancer with an SN-38-antitrop-2 drug conjugate, sacituzumab govitecan. J Clin Oncol. 2017; 35: 2790-97.

Hong S, Kwon J, Kim DW, Lee HJ, Lee D, Mar W. Mulberrofuran G protects ischemic injury‐induced cell death via inhibition of NOX4‐mediated ROS generation and ER stress. Phytother Res. 2017; 31: 321-29.

Khan H, Singh RD, Tiwari R, Gangopadhyay S, Roy SK, Singh D, Srivastava V. Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression. Toxicology 2017; 386: 28-39.

Koirala P, Seong SH, Zhou Y, Shrestha S, Jung HA, Choi JS. Structure activity relationship of the tyrosinase inhibitors kuwanon G, mulberrofuran G, and albanol B from Morus Species: A kinetics and molecular docking study. Molecules (Basel, Switzerland). 2018; 23: 1413.

Li M, Wu X, Wang X, Shen T, Ren D. Two novel compounds from the root bark of Morus alba L. Nat Prod Res. 2018; 32: 36-42.

Li Y, Li Y, Zhang H, Shi R, Zhang Z, Liu H, Chen J. EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation. BMC Pulm Med. 2021; 21: 190.

Liang L, Hui K, Hu C, Wen Y, Yang S, Zhu P, Wang L, Xia Y, Qiao Y, Sun W, Fei J, Chen T, Zhao F, Yang B, Jiang X. Autophagy inhibition potentiates the anti-angiogenic property of multikinase inhibitor anlotinib through JAK2/ STAT3/VEGFA signaling in non-small cell lung cancer cells. J Exp Clin Cancer Res. 2019; 38: 71.

Liang CC, Park AY, Guan JL. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007; 2: 329-33.

Liu R-Y, Zeng Y, Lei Z, Wang L, Yang H, Liu Z, Zhao J, Zhang H-T. JAK/STAT3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells. Int J Oncol. 2014; 44: 1643-51.

Liu X, Chen B, You W, Xue S, Qin H, Jiang H. The membrane bile acid receptor TGR5 drives cell growth and migration via activation of the JAK2/STAT3 signaling pathway in non-small cell lung cancer. Cancer Lett. 2018; 412: 194-207.

Mahmood T, Yang PC. Western blot: Technique, theory, and trouble shooting. North Am J Med Sci. 2012; 4: 429.

Niu G, Wright KL, Ma Y, Wright GM, Huang M, Irby R, Briggs J, Karras J, Cress WD, Pardoll D. Role of Stat3 in regulating p53 expression and function. Mol Cell Biol. 2005; 25: 7432-40.

Patel P, Tsiperson V, Gottesman SR, Somma J, Blain SW. Dual inhibition of CDK4 and CDK2 via targeting p27 tyrosine phosphorylation induces a potent and durable response in breast cancer cells. Mol Cancer Res. 2018; 16: 361-77.

Paudel P, Yu T, Seong SH, Kuk EB, Jung HA, Choi JS. Protein tyrosine phosphatase 1B inhibition and glucose uptake potentials of mulberrofuran G, albanol B, and kuwanon G from root bark of Morus alba L. in insulin-resistant HepG2 cells: An in vitro and in silico study. Int J Mol Sci. 2018; 19: 1542.

Pijuan J, Barceló C, Moreno DF, Maiques O, Sisó P, Marti RM, Macià A, Panosa A. In vitro cell migration, invasion, and adhesion assays: From cell imaging to data analysis. Front Cell Dev Biol. 2019; 7: 107.

Pyo JS, Kim HH, Kim KM, Kang JS. Amelioration of dry eye syndrome by oral administration of cultivated wild ginseng extract. Bangladesh J Pharmacol. 2019; 14: 61-66.

Ramalingam V, Revathidevi S, Shanmuganayagam T, Muthulakshmi L, Rajaram R. Gold nanoparticle induces mitochondria-mediated apoptosis and cell cycle arrest in non-small cell lung cancer cells. Gold Bull. 2017; 50: 177-89.

Shanmugasundaram K, Nayak BK, Friedrichs WE, Kaushik D, Rodriguez R, Block K. NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance. Nat Commun. 2017; 8: 997.

Sherr CJ. D-type cyclins. Trends Biochem Sci. 1995; 20: 187-90.

Singh K, Dong Q, TimiriShanmugam PS, Koul S, Koul HK. Tetrandrine inhibits deregulated cell cycle in pancreatic cancer cells: Differential regulation of p21Cip1/Waf1, p27Kip1 and cyclin D1. Cancer Lett. 2018; 425: 164-73.

Sun D, Shen W, Zhang F, Fan H, Xu C, Li L, Tan J, Miao Y, Zhang H, Yang Y. α-Hederin inhibits interleukin 6-induced epithelial-to-mesenchymal transition associated with disruption of JAK2/STAT3 signaling in colon cancer cells. Biomed Pharmacother. 2018; 101: 107-14.

Szydłowski M, Dębek S, Prochorec-Sobieszek M, Szołkowska M, Tomirotti AM, Juszczyński P, Szumera-Ciećkiewicz A. PIM kinases promote survival and immune escape in primary mediastinal large B-cell lymphoma through modulation of JAK-STAT and NF-κB activity. Am J Pathol. 2021; 191: 567-74.

Tang Y, Tong X, Li Y, Jiang G, Yu M, Chen Y, Dong S. JAK2/STAT3 pathway is involved in the protective effects of epidermal growth factor receptor activation against cerebral ischemia/reperfusion injury in rats. Neurosci Lett. 2018; 662: 219-26.

Vandooren J, Van den Steen PE, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol. 2013; 48: 222-72.

Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity. Proc Natl Acad Sci. 2003; 100: 1879-84.

Weng L, Zhang H, Li X, Zhan H, Chen F, Han L, Xu Y, Cao X. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia. Int Immunopharmacol. 2017; 44: 1-8.

Zhang JF, Wang P, Yan YJ, Li Y, Guan MW, Yu JJ, Wang XD. IL‑33 enhances glioma cell migration and invasion by upregulation of MMP2 and MMP9 via the ST2-NF-κB pathway. Oncol Reports. 2017; 38: 2033-42.

Zhang X, Yin P, Di D, Luo G, Zheng L, Wei J, Zhang J, Shi Y, Zhang J, Xu N. IL-6 regulates MMP-10 expression via JAK2/STAT3 signaling pathway in a human lung adenocarcinoma cell line. Anticancer Res. 2009; 29: 4497-501.

Zhang Y, Wang DC, Shi L, Zhu B, Min Z, Jin J. Genome analyses identify the genetic modification of lung cancer subtypes. Seminars in cancer biology. Elsevier, 2017, pp 20-30.

Downloads

Published

2021-12-26

How to Cite

Guo, H.-Y.-B. ., X.-X. Liu, X.-Y. Zhu, and Z. Yu. “Mulberrofuran G Inhibits Proliferation and Migration by Inactivating JAK2/STAT3 Signaling in Lung Cancer Cells”. Bangladesh Journal of Pharmacology, vol. 16, no. 4, Dec. 2021, pp. 134-40, doi:10.3329/bjp.v16i4.55198.

Issue

Vol. 16 No. 4 (2021)

Section

Research Articles

License

Copyright (c) 2021 Hai-Yuan-Bo Guo, Xiao-Xiao Liu, Xiao-Yong Zhu, Zhe Yu

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).