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Li, Zhong-Rui, Zheng, Yu, Han, Chao, Wang, Lei. (1405). Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line. سامانه مدیریت نشریات علمی, 51(8), 570-581. doi: 10.30476/ijms.2026.109449.4477
Zhong-Rui Li; Yu Zheng; Chao Han; Lei Wang. "Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line". سامانه مدیریت نشریات علمی, 51, 8, 1405, 570-581. doi: 10.30476/ijms.2026.109449.4477
Li, Zhong-Rui, Zheng, Yu, Han, Chao, Wang, Lei. (1405). 'Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line', سامانه مدیریت نشریات علمی, 51(8), pp. 570-581. doi: 10.30476/ijms.2026.109449.4477
Li, Zhong-Rui, Zheng, Yu, Han, Chao, Wang, Lei. Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line. سامانه مدیریت نشریات علمی, 1405; 51(8): 570-581. doi: 10.30476/ijms.2026.109449.4477

Mulberrofuran G Induces Apoptosis and Cell Cycle Arrest Through Suppression of the JAK2/STAT3 Pathway by Direct JAK2 Inhibition and Reactive Oxygen Species Induction in the NCI-H460 Cell Line

Iranian Journal of Medical Sciences
مقاله 5، دوره 51، شماره 8، آبان 2026، صفحه 570-581    اصل مقاله (2.31 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2026.109449.4477
نویسندگان
Zhong-Rui Li1؛ Yu Zheng1؛ Chao Han* 2؛ Lei Wang1
1Department of Rehabilitation, College of Acupuncture and Moxibustion and Massage Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, No. 138 Xianlin Avenue, Nanjing 210023, China
2State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China
چکیده
Background: Large cell lung carcinoma (LCLC) is an aggressive non-small cell lung cancer subtype. Mulberrofuran G (MG) from Morus alba L. possesses pharmacological properties, but its anticancer mechanisms in LCLC remain unexplored. This study aimed to validate the antitumor activity of MG against NCI-H460 cells and elucidate its dual mechanism involving Janus kinase 2 (JAK2) inhibition and reactive oxygen species (ROS) induction.
Methods: This study was conducted at the Nanjing University of Chinese Medicine and China Pharmaceutical University, Nanjing, China, from 2023 to 2025. Cell viability was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Flow cytometry using annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), 2’,7’-dichlorodihydrofluorescein diacetate (DCFH-DA), and 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) measured apoptosis, cell cycle, ROS, and mitochondrial membrane potential (MMP). Western blot analyzed p21, cyclin B1, caspases3/7/9, cleaved caspases3/7/9, poly(ADP-ribose) polymerase (PARP), cleaved PARP, JAK2, p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3. Interactions were confirmed via docking, cellular thermal shift assay, and ADP-Glo. In vivo efficacy was evaluated in zebrafish. Data analysis was performed using GraphPad Prism 8.0. Statistical significance was determined using Student’s t test or one-way/two-way ANOVA followed by Tukey’s post hoc test (P<0.05).
Results: MG suppressed proliferation (IC50=9.90 μM), induced G2/M arrest, and triggered mitochondrial apoptosis. MG inhibited JAK2/STAT3 via direct kinase inhibition (IC50=17.17 μM) and ROS-mediated suppression. N-acetylcysteine (NAC) reversed these effects. Zebrafish tumor growth decreased by 19.7% (P<0.05).
Conclusion: MG exerts anticancer effects against LCLC by inducing ROS accumulation and dual suppression of the JAK2/STAT3 pathway, highlighting its potential as a therapeutic candidate.

تازه های تحقیق

Zhong-Rui Li (Google Scholar) 
Chao Han (Google Scholar) 

کلیدواژه‌ها
Mulberrofuran G؛ Reactive oxygen species؛ Janus kinase 2؛ STAT3 Transcription factor
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