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OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma

  • Authors:
    • Kaiwen Shen
    • Xinglin Jin
  • View Affiliations / Copyright

    Affiliations: Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, P.R. China
    Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 361
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    Published online on: May 22, 2025
       https://doi.org/10.3892/ol.2025.15107
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Abstract

Apoptosis is one of the primary mechanisms by which anticancer drugs exert their effects. Orsaponin (OSW‑1) is a natural broad‑spectrum inhibitor of enterovirus replication isolated from Ornithogalum saundersiae. It is a specific antagonist of cholesterol‑binding protein (OSBP) and OSBP‑related protein 4 (ORP4). OSW‑1 exhibits antitumor activity; however, its mechanism remains to be elucidated. The present study aimed to explore the cytotoxicity of OSW‑1 in hepatocellular carcinoma (HCC) and its antitumor mechanisms. Gene Expression Profiling Interactive Analysis database analysis showed that uncoupling protein 2 (UCP2) expression was markedly higher in HCC tissue. Mitochondrial membrane potential and cell cycle progression in Hep3B cells were assessed by flow cytometry using JC‑1 and propidium iodide staining, respectively. OSW‑1 decreased mitochondrial membrane potential, induced cell cycle arrest at the G2/M phase and caused production of intracellular reactive oxygen species. Western blot and quantitative PCR determined that OSW‑1 induced apoptosis in Hep3B cells by downregulating UCP2 expression. These results suggest that OSW‑1 has potential as a therapeutic agent for liver cancer. Future studies should explore its effects on a broader range of HCC cell lines and in vivo models and investigate its molecular mechanisms and side effects.
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1 

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W and He J: Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 4:47–53. 2024. View Article : Google Scholar : PubMed/NCBI

2 

Wang X, Meng F and Mao J: Progress of natural sesquiterpenoids in the treatment of hepatocellular carcinoma. Front Oncol. 14:14452222024. View Article : Google Scholar : PubMed/NCBI

3 

Wang B, Hao X, Yan J, Li X, Zhao M and Han T: A bibliometric analysis of immune-related adverse events in cancer patients and a meta-analysis of immune-related adverse events in patients with hepatocellular carcinoma. J Transl Int Med. 12:225–243. 2024.PubMed/NCBI

4 

Hadkar VM, Mohanty C and Selvaraj CI: Biopolymeric nanocarriers in cancer therapy: Unleashing the potency of bioactive anticancer compounds for enhancing drug delivery. RSC Adv. 14:25149–25173. 2024. View Article : Google Scholar : PubMed/NCBI

5 

Yao Y, Chen Y, Yao T, Li C, Li S and Wang N: Anticancer effects of OSW-1 on colorectal cancer cells via the ROS/NLRP3/caspase-1 pyroptosis signaling pathway. Int Immunopharmacol. 148:1140542025. View Article : Google Scholar : PubMed/NCBI

6 

Zhan Z, Liu Z, Zhang C, Gao H, Lai J, Chen Y and Huang H: Anticancer effects of OSW-1 on glioma cells via regulation of the PI3K/AKT signal pathway: A network pharmacology approach and experimental validation in vitro and in vivo. Front Pharmacol. 13:9671412022. View Article : Google Scholar : PubMed/NCBI

7 

Zhan Z, Liu Z, Lai J, Zhang C, Chen Y and Huang H: Anticancer effects and mechanisms of OSW-1 isolated from Ornithogalum saundersiae: A review. Front Oncol. 11:7477182021. View Article : Google Scholar : PubMed/NCBI

8 

Garcia-Prieto C, Riaz Ahmed KB, Chen Z, Zhou Y, Hammoudi N, Kang Y, Lou C, Mei Y, Jin Z and Huang P: Effective killing of leukemia cells by the natural product OSW-1 through disruption of cellular calcium homeostasis. J Biol Chem. 288:3240–3250. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Lee HY, Nga HT, Tian J and Yi HS: Mitochondrial metabolic signatures in hepatocellular carcinoma. Cells. 10:19012021. View Article : Google Scholar : PubMed/NCBI

10 

Zeng L, Zhu L, Fu S, Li Y and Hu K: Mitochondrial dysfunction-molecular mechanisms and potential treatment approaches of hepatocellular carcinoma. Mol Cell Biochem. 480:2131–2142. 2025. View Article : Google Scholar : PubMed/NCBI

11 

Szewczyk A, Jarmuszkiewicz W, Koziel A, Sobieraj I, Nobik W, Lukasiak A, Skup A, Bednarczyk P, Drabarek B, Dymkowska D, et al: Mitochondrial mechanisms of endothelial dysfunction. Pharmacol Rep. 67:704–710. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Yu G, Liu J, Xu K and Dong J: Uncoupling protein 2 mediates resistance to gemcitabine-induced apoptosis in hepatocellular carcinoma cell lines. Biosci Rep. 35:e002312015. View Article : Google Scholar : PubMed/NCBI

13 

Jin J, Jin X, Qian C, Ruan Y and Jiang H: Signaling network of OSW-1-induced apoptosis and necroptosis in hepatocellular carcinoma. Mol Med Rep. 7:1646–1650. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Perelman A, Wachtel C, Cohen M, Haupt S, Shapiro H and Tzur A: JC-1: Alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis. 22:e4302012. View Article : Google Scholar : PubMed/NCBI

16 

Kubo S, Mimaki Y, Terao M, Sashida Y, Nikaido T and Ohmoto T: Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae. Phytochemistry. 31:3969–3973. 1992. View Article : Google Scholar

17 

Ding X, Li Y, Li J and Yin Y: OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer. Cancer Med. 9:5558–5569. 2020. View Article : Google Scholar : PubMed/NCBI

18 

Wang N, Li CY, Yao TF, Kang XD and Guo HS: OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1-p62/SQSTM1 complex. World J Gastroenterol. 30:2155–2174. 2024. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Y, Fang F, Fan K, Zhang Y, Zhang J, Guo H, Yu P and Ma J: Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo. Oncol Rep. 37:3509–3519. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Zhang C, Zhao Y, Yu M, Qin J, Ye B and Wang Q: Mitochondrial dysfunction and chronic liver disease. Curr Issues Mol Biol. 44:3156–3165. 2022. View Article : Google Scholar : PubMed/NCBI

21 

Serviddio G, Bellanti F, Tamborra R, Rollo T, Capitanio N, Romano AD, Sastre J, Vendemiale G and Altomare E: Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut. 57:957–965. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Nesci S and Rubattu SL: UCP2, a member of the mitochondrial uncoupling proteins: An overview from physiological to pathological roles. Biomedicines. 12:13072024. View Article : Google Scholar : PubMed/NCBI

23 

Yu G, Wang J, Xu K and Dong J: Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma. Biosci Rep. 36:e003352016. View Article : Google Scholar : PubMed/NCBI

24 

Iguchi T, Kuroda M, Naito R, Watanabe T, Matsuo Y, Yokosuka A and Mimaki Y: Cholestane glycosides from Ornithogalum saundersiae bulbs and the induction of apoptosis in HL-60 cells by OSW-1 through a mitochondrial-independent signaling pathway. J Nat Med. 73:131–145. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Wu M, Huang Q, Liao M, Wu X, Xi H, Ma H, Li S, Zhang Y and Xia Y: OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis. Cell Oncol (Dordr). 45:1255–1275. 2022. View Article : Google Scholar : PubMed/NCBI

26 

Zhao P, Li X, Yang Q, Lu Y, Wang G, Yang H, Dong J and Zhang H: Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-α/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice. Front Pharmacol. 13:10388022023. View Article : Google Scholar : PubMed/NCBI

27 

Qiao C, Wei L, Dai Q, Zhou Y, Yin Q, Li Z, Xiao Y, Guo Q and Lu N: UCP2-related mitochondrial pathway participates in oroxylin A-induced apoptosis in human colon cancer cells. J Cell Physiol. 230:1054–1063. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Yu J, Shi L, Lin W, Lu B and Zhao Y: UCP2 promotes proliferation and chemoresistance through regulating the NF-κB/β-catenin axis and mitochondrial ROS in gallbladder cancer. Biochem Pharmacol. 172:1137452020. View Article : Google Scholar : PubMed/NCBI

29 

El-Khoury TG, Bahr GM and Echtay KS: Muramyl-dipeptide-induced mitochondrial proton leak in macrophages is associated with upregulation of uncoupling protein 2 and the production of reactive oxygen and reactive nitrogen species. FEBS J. 278:3054–3064. 2011. View Article : Google Scholar : PubMed/NCBI

30 

El Hoss S, Bahr GM and Echtay KS: Lopimune-induced mitochondrial toxicity is attenuated by increased uncoupling protein-2 level in treated mouse hepatocytes. Biochem J. 468:401–407. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Kukat A, Dogan SA, Edgar D, Mourier A, Jacoby C, Maiti P, Mauer J, Becker C, Senft K, Wibom R, et al: Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity. PLoS Genet. 10:e10043852014. View Article : Google Scholar : PubMed/NCBI

32 

Morihara H, Yamada T, Tona Y, Akasaka M, Okuyama H, Chatani N, Shinonome S, Ueyama A and Kuwabara K: Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis. PLoS One. 19:e03059842024. View Article : Google Scholar : PubMed/NCBI

33 

Ni K, Li ZL, Hu ZY and Hong L: Antitumor effect of apcin on endometrial carcinoma via p21-mediated cell cycle arrest and apoptosis. Curr Med Sci. 44:623–632. 2024. View Article : Google Scholar : PubMed/NCBI

34 

Abusaliya A, Jeong SH, Bhosale PB, Kim HH, Park MY, Kim E, Won CK, Park KI, Heo JD, Kim HW, et al: Mechanistic action of cell cycle arrest and intrinsic apoptosis via inhibiting Akt/mTOR and activation of p38-MAPK signaling pathways in hep3B liver cancer cells by prunetrin-a flavonoid with therapeutic potential. Nutrients. 15:34072023. View Article : Google Scholar : PubMed/NCBI

35 

Liu CH, Huang ZH, Dong XY, Zhang XQ, Li YH, Zhao G, Sun BS and Shen YN: Inhibition of uncoupling protein 2 enhances the radiosensitivity of cervical cancer cells by promoting the production of reactive oxygen specie. Oxid Med Cell Longev. 2011:18417832021. View Article : Google Scholar : PubMed/NCBI

36 

Hu C, Zhang X, Wei W, Zhang N, Wu H, Ma Z, Li L, Deng W and Tang Q: Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via maintaining AMPKα/UCP2 pathway. Acta Pharm Sin B. 9:690–701. 2019. View Article : Google Scholar : PubMed/NCBI

37 

Lou J, Wang Y, Wang X and Jiang Y: Uncoupling protein 2 regulates palmitic acid-induced hepatoma cell autophagy. Biomed Res Int. 2014:8104012014. View Article : Google Scholar : PubMed/NCBI

38 

Derdak Z, Garcia TA and Baffy G: Detection of uncoupling protein-2 (UCP2) as a mitochondrial modulator of apoptosis. Methods Mol Biol. 559:205–217. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shen K and Jin X: OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma. Oncol Lett 30: 361, 2025.
APA
Shen, K., & Jin, X. (2025). OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma. Oncology Letters, 30, 361. https://doi.org/10.3892/ol.2025.15107
MLA
Shen, K., Jin, X."OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma". Oncology Letters 30.1 (2025): 361.
Chicago
Shen, K., Jin, X."OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma". Oncology Letters 30, no. 1 (2025): 361. https://doi.org/10.3892/ol.2025.15107
Copy and paste a formatted citation
x
Spandidos Publications style
Shen K and Jin X: OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma. Oncol Lett 30: 361, 2025.
APA
Shen, K., & Jin, X. (2025). OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma. Oncology Letters, 30, 361. https://doi.org/10.3892/ol.2025.15107
MLA
Shen, K., Jin, X."OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma". Oncology Letters 30.1 (2025): 361.
Chicago
Shen, K., Jin, X."OSW‑1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma". Oncology Letters 30, no. 1 (2025): 361. https://doi.org/10.3892/ol.2025.15107
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