Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Cinobufotalin Induces Ferroptosis to Suppress Lung Cancer Cell Growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC Pathway via Resibufogenin

Author(s): Junming Huang, Caijiu Deng, Tianshen Guo, Xiaofeng Chen, Peixi Chen, Shaoshan Du and Meizhen Lu*

Volume 23, Issue 6, 2023

Published on: 28 October, 2022

Page: [717 - 725] Pages: 9

DOI: 10.2174/1871520622666221010092922

Price: $65

Abstract

Background: Lung cancer is the leading cause of cancer-associated death and the first most diagnosed cancer in the world. More than 2 million new cases are diagnosed and 1.6 million people die due to lung cancer every year. It is urgent to explore novel drugs and approaches for lung cancer treatment. Cinobufotalin is a TCM isolated from dried toad venom, which has been used to treat lung cancer. However, the precise mechanism remains unclear.

Objective: This study was to investigate the mechanism of cinobufotalin treated in lung cancer.

Methods: Cell growth was identified by Cell Counting Kit-8 (CCK-8) assay. Besides, ferroptosis of lung cancer cells was determined by intracellular iron content, lactate dehydrogenase (LDH) release and mitochondrial membrane potential. Moreover, RNA levels and proteins were detected by quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB), respectively. In addition, the regulatory effect of hsa-miR-367-3p on TFRC was confirmed by luciferase reporter assay.

Results: This study indicated that cinobufotalin suppressed lung cancer cell growth through resibufogenin. Besides, cinobufotalin induced ferroptosis in lung cancer cells through resibufogenin. Moreover, cinobufotalin increased lncRNA LINC00597 level, whereas it downregulated hsa-miR-367-3p expression in lung cancer cells via resibufogenin. In addition, ferroptosis inducer transferrin receptor (TFRC) was the target of hsa-miR-367-3p, and lncRNA LINC00597 upregulates TFRC expression through sponging hsa-miR-367-3p in lung cancer cells.

Conclusion: In summary, this study indicated that cinobufotalin induced ferroptosis to suppress lung cancer cell growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC pathway via resibufogenin might provide novel therapeutic targets for lung cancer therapy.

« Previous Next »
Graphical Abstract

[1]
Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2020, 70(4), 313.
[http://dx.doi.org/10.3322/caac.21609] [PMID: 32767693]
[2]
Nasim, F.; Sabath, B.F.; Eapen, G.A. Lung Cancer. Med. Clin. North Am., 2019, 103(3), 463-473.
[http://dx.doi.org/10.1016/j.mcna.2018.12.006] [PMID: 30955514]
[3]
Cao, M.; Chen, W. Epidemiology of lung cancer in China. Thorac. Cancer, 2019, 10(1), 3-7.
[http://dx.doi.org/10.1111/1759-7714.12916] [PMID: 30485694]
[4]
Hirsch, F.R.; Scagliotti, G.V.; Mulshine, J.L.; Kwon, R.; Curran, W.J., Jr; Wu, Y.L.; Paz-Ares, L. Lung cancer: Current therapies and new targeted treatments. Lancet, 2017, 389(10066), 299-311.
[http://dx.doi.org/10.1016/S0140-6736(16)30958-8] [PMID: 27574741]
[5]
Herbst, R.S.; Morgensztern, D.; Boshoff, C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689), 446-454.
[http://dx.doi.org/10.1038/nature25183] [PMID: 29364287]
[6]
Jones, G.S.; Baldwin, D.R. Recent advances in the management of lung cancer. Clin. Med., 2018, 18(Suppl. 2), s41-s46.
[http://dx.doi.org/10.7861/clinmedicine.18-2-s41] [PMID: 29700092]
[7]
Ruiz-Cordero, R.; Devine, W.P. Targeted therapy and checkpoint immunotherapy in lung cancer. Surg. Pathol. Clin., 2020, 13(1), 17-33.
[http://dx.doi.org/10.1016/j.path.2019.11.002] [PMID: 32005431]
[8]
Su, X.L.; Wang, J.W.; Che, H.; Wang, C.F.; Jiang, H.; Lei, X.; Zhao, W.; Kuang, H.X.; Wang, Q.H. Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer. Chin. Med. J., 2020, 133(24), 2987-2997.
[http://dx.doi.org/10.1097/CM9.0000000000001141] [PMID: 33065603]
[9]
Li, Z.; Feiyue, Z.; Gaofeng, L. Traditional Chinese medicine and lung cancer-From theory to practice. Biomed. Pharmacother., 2021, 137, 111381.
[http://dx.doi.org/10.1016/j.biopha.2021.111381] [PMID: 33601147]
[10]
Zhang, X.W.; Liu, W.; Jiang, H.L.; Mao, B. Chinese herbal medicine for advanced non-small-cell lung cancer: A systematic review and meta-analysis. Am. J. Chin. Med., 2018, 46(5), 923-952.
[http://dx.doi.org/10.1142/S0192415X18500490] [PMID: 30001642]
[11]
Meng, Z.; Yang, P.; Shen, Y.; Bei, W.; Zhang, Y.; Ge, Y.; Newman, R.A.; Cohen, L.; Liu, L.; Thornton, B.; Chang, D.Z.; Liao, Z.; Kurzrock, R. Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. Cancer, 2009, 115(22), 5309-5318.
[http://dx.doi.org/10.1002/cncr.24602] [PMID: 19701908]
[12]
Emam, H.; Zhao, Q.L.; Furusawa, Y.; Refaat, A.; Ahmed, K.; Kadowaki, M.; Kondo, T. Apoptotic cell death by the novel natural compound, cinobufotalin. Chem. Biol. Interact., 2012, 199(3), 154-160.
[http://dx.doi.org/10.1016/j.cbi.2012.07.005] [PMID: 22898211]
[13]
Li, L.L.; Su, Y.X.; Mao, Y.; Jiang, P.Y.; Chu, X.L.; Xue, P.; Jia, B.H.; Zhu, S.J. The effectiveness and safety of cinobufotalin injection as an adjunctive treatment for lung cancer: A meta-analysis of randomized controlled trials. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-17.
[http://dx.doi.org/10.1155/2021/8852261] [PMID: 33628320]
[14]
Han, Y.; Ma, R.; Cao, G.; Liu, H.; He, L.; Tang, L.; Li, H.; Luo, Q. Combined treatment of cinobufotalin and gefitinib exhibits potent efficacy against lung cancer. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-9.
[http://dx.doi.org/10.1155/2021/6612365] [PMID: 34122599]
[15]
Zhang, F.; Yin, Y.; Xu, T. Cinobufotalin injection combined with chemotherapy for the treatment of advanced NSCLC in China. Medicine, 2019, 98(35), e16969.
[http://dx.doi.org/10.1097/MD.0000000000016969] [PMID: 31464940]
[16]
Ichikawa, M.; Sowa, Y.; Iizumi, Y.; Aono, Y.; Sakai, T. Resibufogenin induces G1-phase arrest through the proteasomal degradation of cyclin D1 in human malignant tumor cells. PLoS One, 2015, 10(6), e0129851.
[http://dx.doi.org/10.1371/journal.pone.0129851] [PMID: 26121043]
[17]
Han, Q.; Ma, Y.; Wang, H.; Dai, Y.; Chen, C.; Liu, Y.; Jing, L.; Sun, X. Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis. J. Transl. Med., 2018, 16(1), 201.
[http://dx.doi.org/10.1186/s12967-018-1580-x] [PMID: 30029665]
[18]
Feng, C.; Zhao, Y.; Li, Y.; Zhang, T.; Ma, Y.; Liu, Y. LncRNA MALAT1 promotes lung cancer proliferation and gefitinib resistance by acting as a miR-200a sponge. Arch. Bronconeumol., 2019, 55(12), 627-633.
[http://dx.doi.org/10.1016/j.arbres.2019.03.026] [PMID: 31133357]
[19]
Qian, H.; Chen, L.; Huang, J.; Wang, X.; Ma, S.; Cui, F.; Luo, L.; Ling, L.; Luo, K.; Zheng, G. The lncRNA MIR4435-2HG promotes lung cancer progression by activating β-catenin signalling. J. Mol. Med., 2018, 96(8), 753-764.
[http://dx.doi.org/10.1007/s00109-018-1654-5] [PMID: 29872866]
[20]
Li, D.; Zhong, M.; Su, Q.; Song, F.; Xie, T.; He, J.; Wei, J.; Lu, G.; Hu, X.; Wei, G. Active fraction of Polyrhachis vicina Rogers (AFPR) suppressed breast cancer growth and progression via regulating EGR1/lncRNA-NKILA/NF-κB axis. Biomed. Pharmacother., 2020, 123, 109616.
[http://dx.doi.org/10.1016/j.biopha.2019.109616] [PMID: 31881485]
[21]
Lv, C.; Wu, X.; Wang, X.; Su, J.; Zeng, H.; Zhao, J.; Lin, S.; Liu, R.; Li, H.; Li, X.; Zhang, W. The gene expression profiles in response to 102 traditional Chinese medicine (TCM) components: A general template for research on TCMs. Sci. Rep., 2017, 7(1), 352.
[http://dx.doi.org/10.1038/s41598-017-00535-8] [PMID: 28336967]
[22]
Wang, M.; Mao, C.; Ouyang, L.; Liu, Y.; Lai, W.; Liu, N.; Shi, Y.; Chen, L.; Xiao, D.; Yu, F.; Wang, X.; Zhou, H.; Cao, Y.; Liu, S.; Yan, Q.; Tao, Y.; Zhang, B. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ., 2019, 26(11), 2329-2343.
[http://dx.doi.org/10.1038/s41418-019-0304-y] [PMID: 30787392]
[23]
Bersuker, K.; Hendricks, J.M.; Li, Z.; Magtanong, L.; Ford, B.; Tang, P.H.; Roberts, M.A.; Tong, B.; Maimone, T.J.; Zoncu, R.; Bassik, M.C.; Nomura, D.K.; Dixon, S.J.; Olzmann, J.A. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature, 2019, 575(7784), 688-692.
[http://dx.doi.org/10.1038/s41586-019-1705-2] [PMID: 31634900]
[24]
Du, J.; Wang, L.; Huang, X.; Zhang, N.; Long, Z.; Yang, Y. Shuganning injection, a traditional Chinese patent medicine, induces ferroptosis and suppresses tumor growth in triple-negative breast cancer cells. Phytomedicine, 2021, 85, 153551.
[25]
Wang, Y.; Chen, Q.; Shi, C.; Jiao, F.; Gong, Z. Mechanism of glycyrrhizin on ferroptosis during acute liver failure by inhibiting oxidative stress. Mol. Med. Rep., 2019, 20(5), 4081-4090.
[http://dx.doi.org/10.3892/mmr.2019.10660] [PMID: 31545489]
[26]
Wu, L.; Liu, M.; Liang, J.; Li, N.; Yang, D.; Cai, J.; Zhang, Y.; He, Y.; Chen, Z.; Ma, T. Ferroptosis as a new mechanism in Parkinson’s disease therapy using traditional chinese medicine. Front. Pharmacol., 2021, 12, 659584.
[http://dx.doi.org/10.3389/fphar.2021.659584] [PMID: 34163356]
[27]
Zhang, X.; Cheng, Y.; Zhou, Q.; Huang, H.; Dong, Y.; Yang, Y.; Zhao, M.; He, Q. The effect of Chinese Traditional Medicine Huaiqihuang (HQH) on the protection of nephropathy. Oxid. Med. Cell. Longev., 2020, 2020, 1-10.
[http://dx.doi.org/10.1155/2020/2153912] [PMID: 32655761]
[28]
Chen, P.; Wu, Q.; Feng, J.; Yan, L.; Sun, Y.; Liu, S.; Xiang, Y.; Zhang, M.; Pan, T.; Chen, X.; Duan, T.; Zhai, L.; Zhai, B.; Wang, W.; Zhang, R.; Chen, B.; Han, X.; Li, Y.; Chen, L.; Liu, Y.; Huang, X.; Jin, T.; Zhang, W.; Luo, H.; Chen, X.; Li, Y.; Li, Q.; Li, G.; Zhang, Q.; Zhuo, L.; Yang, Z.; Tang, H.; Xie, T.; Ouyang, X.; Sui, X. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis. Signal Transduct. Target. Ther., 2020, 5(1), 51.
[http://dx.doi.org/10.1038/s41392-020-0149-3] [PMID: 32382060]
[29]
Lou, J.S.; Zhao, L.P.; Huang, Z.H.; Chen, X.Y.; Xu, J.T.; Tai, W.C.S.; Tsim, K.W.K.; Chen, Y.T.; Xie, T. Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer. Phytomedicine, 2021, 80, 153370.
[http://dx.doi.org/10.1016/j.phymed.2020.153370] [PMID: 33113504]
[30]
Bei, W.J.; Guo, J.; Wu, H.Y.; Cao, Y. Lipid-regulating effect of traditional chinese medicine: Mechanisms of actions. Evid. Based Complement. Alternat. Med., 2012, 2012, 1-10.
[http://dx.doi.org/10.1155/2012/970635] [PMID: 22611438]
[31]
Vijayakumar, M.V.; Pandey, V.; Mishra, G.C.; Bhat, M.K. Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat accumulation and upregulation of LDL receptor. Obesity (Silver Spring), 2010, 18(4), 667-674.
[http://dx.doi.org/10.1038/oby.2009.337] [PMID: 19851306]
[32]
Xiao, C.; Zhou, J.; He, Y.; Jia, H.; Zhao, L.; Zhao, N.; Lu, A. Effects of triptolide from Radix tripterygium wilfordii (Leigongteng) on cartilage cytokines and transcription factor NF-κB: A study on induced arthritis in rats. Chin. Med., 2009, 4(1), 13.
[http://dx.doi.org/10.1186/1749-8546-4-13] [PMID: 19570240]
[33]
Yu, Q.; Luo, J.; Zhang, J.; Chen, Y.; Chen, K.; Lin, J.; Sun, S.; Lin, X. Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene SGK3 downregulation. Am. J. Transl. Res., 2020, 12(9), 5538-5550.
[PMID: 33042436]
[34]
Guo, Y.; Liang, F.; Zhao, F.; Zhao, J. Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer. Mol. Cell. Biochem., 2020, 466(1-2), 103-115.
[http://dx.doi.org/10.1007/s11010-020-03692-z] [PMID: 32006291]
[35]
Li, Y.; Zhu, H.C.; Du, Y.; Zhao, H.; Wang, L. Silencing lncRNA SLC16A1-AS1 induced ferroptosis in renal cell carcinoma through miR-143-3p/SLC7A11 signaling. Technol. Cancer Res. Treat., 2022, 21.
[http://dx.doi.org/10.1177/15330338221077803] [PMID: 35167383]
[36]
Chen, R.; Zhang, C.; Cheng, Y.; Wang, S.; Lin, H.; Zhang, H. LncRNA UCC promotes epithelial–mesenchymal transition via the miR-143-3p/SOX5 axis in non-small-cell lung cancer. Lab. Invest., 2021, 101(9), 1153-1165.
[http://dx.doi.org/10.1038/s41374-021-00586-6] [PMID: 33824420]
[37]
Yang, J.; Jia, Y.; Wang, B.; Yang, S.; Du, K.; Luo, Y.; Li, Y.; Zhu, B. Circular RNA TUBA1C accelerates the progression of non-small-cell lung cancer by sponging miR-143-3p. Cell. Signal., 2020, 74, 109693.
[http://dx.doi.org/10.1016/j.cellsig.2020.109693] [PMID: 32599139]
[38]
Lu, T.; Qiu, T.; Han, B.; Wang, Y.; Sun, X.; Qin, Y.; Liu, A.; Ge, N.; Jiao, W. Circular RNA circCSNK1G3 induces HOXA10 signaling and promotes the growth and metastasis of lung adenocarcinoma cells through hsa-miR-143-3p sponging. Cell. Oncol., 2021, 44(2), 297-310.
[http://dx.doi.org/10.1007/s13402-020-00565-x] [PMID: 33118120]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy