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image of The Molecular Mechanism of a Complex1-Induced Apoptosis in Cancer Cells of the Esophagus

Abstract

Background

Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109).

Objective

This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells.

Methods

EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting.

Results

Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-L-cysteine(NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity.

Conclusion

Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.

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2025-02-18
2025-03-15
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References

  1. Short M.W. Burgers K.G. Fry V.T. Esophageal cancer. Am. Fam. Physician 2017 95 1 22 28 28075104
    [Google Scholar]
  2. Teng Y. Xia C. Cao M. Yang F. Yan X. He S. Cao M. Zhang S. Li Q. Tan N. Wang J. Chen W. Esophageal cancer global burden profiles, trends, and contributors. Cancer Biol. Med. 2024 21 8 1 11 10.20892/j.issn.2095‑3941.2024.0145 39066471
    [Google Scholar]
  3. Morgan E. Soerjomataram I. Rumgay H. Coleman H.G. Thrift A.P. Vignat J. Laversanne M. Ferlay J. Arnold M. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: New estimates from GLOBOCAN 2020. Gastroenterology 2022 163 3 649 658.e2 10.1053/j.gastro.2022.05.054 35671803
    [Google Scholar]
  4. He F. Wang J. Liu L. Qin X. Wan Z. Li W. Ping Z. Esophageal cancer: Trends in incidence and mortality in China from 2005 to 2015. Cancer Med. 2021 10 5 1839 1847 10.1002/cam4.3647 33594825
    [Google Scholar]
  5. Zhang Y. Epidemiology of esophageal cancer. World J. Gastroenterol. 2013 19 34 5598 5606 10.3748/wjg.v19.i34.5598 24039351
    [Google Scholar]
  6. Blaja S.P. Lungu L.V. Kuchkova K.I. Ciocarlan A.G. Barba A.N. Vornicu N. Aricu A.N. Norlabdane compounds containing thiosemicarbazone or 1,3-thiazole fragments: Synthesis and antimicrobial activity. Chem. Nat. Compd. 2021 57 1 101 110 10.1007/s10600‑021‑03292‑3
    [Google Scholar]
  7. Aljahdali M.S. El-Sherif A.A. Synthesis and biological evaluation of novel Zn(II) and Cd(II) Schiff base complexes as antimicrobial, antifungal, and antioxidant agents. Bioinorg. Chem. Appl. 2020 2020 1 17 10.1155/2020/8866382
    [Google Scholar]
  8. Shipman C. Jr Smith S.H. Drach J.C. Klayman D.L. Thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model. Antiviral Res. 1986 6 4 197 222 10.1016/0166‑3542(86)90002‑1 3017201
    [Google Scholar]
  9. Khan A. Paul K. Singh I. Jasinski J.P. Smolenski V.A. Hotchkiss E.P. Kelley P.T. Shalit Z.A. Kaur M. Banerjee S. Roy P. Sharma R. Copper( i ) and silver( i ) complexes of anthraldehyde thiosemicarbazone: Synthesis, structure elucidation, in vitro anti-tuberculosis/cytotoxic activity and interactions with DNA/HSA. Dalton Trans. 2020 49 47 17350 17367 10.1039/D0DT03104F 33210698
    [Google Scholar]
  10. dos Santos T.A.R. da Silva A.C. Silva E.B. Gomes P.A.T.M. Espíndola J.W.P. Cardoso M.V.O. Moreira D.R.M. Leite A.C.L. Pereira V.R.A. Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-Thiazoles in Jurkat and HT-29 cells. Biomed. Pharmacother. 2016 82 555 560 10.1016/j.biopha.2016.05.038 27470396
    [Google Scholar]
  11. Nyawade E.A. Sibuyi N.R.S. Meyer M. Lalancette R. Onani M.O. Synthesis, characterization and anticancer activity of new 2-acetyl-5-methyl thiophene and cinnamaldehyde thiosemicarbazones and their palladium(II) complexes. Inorg. Chim. Acta 2021 515 120036 10.1016/j.ica.2020.120036
    [Google Scholar]
  12. Sibuh B.Z. Khanna S. Taneja P. Sarkar P. Taneja N.K. Molecular docking, synthesis and anticancer activity of thiosemicarbazone derivatives against MCF-7 human breast cancer cell line. Life Sci. 2021 273 119305 10.1016/j.lfs.2021.119305 33675898
    [Google Scholar]
  13. Carcelli M. Tegoni M. Bartoli J. Marzano C. Pelosi G. Salvalaio M. Rogolino D. Gandin V. In vitro and in vivo anticancer activity of tridentate thiosemicarbazone copper complexes: Unravelling an unexplored pharmacological target. Eur. J. Med. Chem. 2020 194 112266 10.1016/j.ejmech.2020.112266 32248006
    [Google Scholar]
  14. Lobana T.S. Kumari P. Zeller M. Butcher R.J. The influence of the substituents at N1 nitrogen on geometry of nickel(II) complexes with heterocyclic thiosemicarbazones. Inorg. Chem. Commun. 2008 11 9 972 974 10.1016/j.inoche.2008.04.032
    [Google Scholar]
  15. Chandra S. Kumar A. Electronic, epr and magnetic studies of Co(II), Ni(II) and Cu(II) complexes with thiosemicarbazone (L1) and semicarbazone (L2) derived from pyrole-2-carboxyaldehyde. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2007 67 3-4 697 701 10.1016/j.saa.2006.07.051 16997618
    [Google Scholar]
  16. Keogan D. Griffith D. Current and potential applications of bismuth-based drugs. Molecules 2014 19 9 15258 15297 10.3390/molecules190915258 25251194
    [Google Scholar]
  17. Zhang L.Z. An G.Y. Yang M. Li M.X. Zhu X.F. Synthesis, characterization, crystal structure and biological activities of the unusual main group 8-coordinate bismuth (III) complex derived from 2-acetylpyrazine N4- pyridylthiosemicarbazone. Inorg. Chem. Commun. 2012 20 37 40 10.1016/j.inoche.2012.02.009
    [Google Scholar]
  18. Li M. Lu Y. Yang M. Li Y. Zhang L. Xie S. One dodecahedral bismuth(iii) complex derived from 2-acetylpyridine N(4)-pyridylthiosemicarbazone: Synthesis, crystal structure and biological evaluation. Dalton Trans. 2012 41 41 12882 12887 10.1039/c2dt31256e 22986888
    [Google Scholar]
  19. Li M.X. Zhang L.Z. Yang M. Niu J.Y. Zhou J. Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone. Bioorg. Med. Chem. Lett. 2012 22 7 2418 2423 10.1016/j.bmcl.2012.02.024 22401862
    [Google Scholar]
  20. Li M.X. Yang M. Niu J.Y. Zhang L.Z. Xie S.Q. A nine-coordinated bismuth(III) complex derived from pentadentate 2,6-diacetylpyridine bis((4)N-methylthiosemicarbazone): crystal structure and both in vitro and in vivo biological evaluation. Inorg. Chem. 2012 51 22 12521 12526 10.1021/ic301959z 23136979
    [Google Scholar]
  21. Li Y.K. Yang M. Li M.X. Yu H. Wu H.C. Xie S.Q. Synthesis, crystal structure and biological evaluation of a main group seven-coordinated bismuth(III) complex with 2-acetylpyridine N4-phenylthiosemicarbazone. Bioorg. Med. Chem. Lett. 2013 23 8 2288 2292 10.1016/j.bmcl.2013.02.097 23489627
    [Google Scholar]
  22. Wang S.H Guo S. Guo J. Du Q.Y. Wu C. Wu Y.K Zhang Y. Cell death pathways: Molecular mechanisms and therapeutic targets for cancer. MedComm 2024 5 9 e693 10.1002/mco2.693
    [Google Scholar]
  23. Zhou G. Shimura T. Yoneima T. Nagamachi A. Kanai A. Doi K. Sasatani M. Age-dependent differences in radiation-induced DNA damage responses in intestinal stem cells. Int. J. Mol. Sci. 2024 25 18 10213 10.3390/ijms251810213 39337697
    [Google Scholar]
  24. Nikoletopoulou V. Markaki M. Palikaras K. Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim. Biophys. Acta Mol. Cell Res. 2013 1833 12 3448 3459 10.1016/j.bbamcr.2013.06.001 23770045
    [Google Scholar]
  25. Rojas-Rivera D. Beltrán S. Muñoz-Carvajal F. Ahumada-Montalva P. Abarzúa L. Gomez L. Hernandez F. Bergmann C.A. Labrador L. Calegaro-Nassif M. Bertrand M.J.M. Manque P.A. Woehlbier U. The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis. Autophagy 2024 20 11 2444 2459 10.1080/15548627.2024.2367923 38873940
    [Google Scholar]
  26. Xu W. Jing L. Wang Q. Lin C.C. Chen X. Diao J. Liu Y. Sun X. Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. Oncotarget 2015 6 30 30017 30034 10.18632/oncotarget.5013 26356820
    [Google Scholar]
  27. Panritdum P. Muangnoi C. Tuntipopipat S. Charoenkiatkul S. Sukprasansap M. Cleistocalyx nervosum var. paniala berry extract and cyaniding‐3‐glucoside inhibit hepatotoxicity and apoptosis. Food Sci. Nutr. 2024 12 4 2947 2962 10.1002/fsn3.3975 38628219
    [Google Scholar]
  28. Zhang D.M. Liu J.S. Deng L.J. Chen M.F. Yiu A. Cao H.H. Tian H.Y. Fung K.P. Kurihara H. Pan J.X. Ye W.C. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis 2013 34 6 1331 1342 10.1093/carcin/bgt060 23393227
    [Google Scholar]
  29. Signore M. Ricci-Vitiani L. De Maria R. Targeting apoptosis pathways in cancer stem cells. Cancer Lett. 2013 332 2 374 382 10.1016/j.canlet.2011.01.013 21315505
    [Google Scholar]
  30. Huang J. Wang J. Song G. Hu C. Xu Z. Chen Z. Xu C. Yang D. Antiproliferative evaluation of novel 4-imidazolidinone derivatives as anticancer agent which triggers ros-dependent apoptosis in colorectal cancer cell. Molecules 2022 27 24 8844 10.3390/molecules27248844 36557977
    [Google Scholar]
  31. Szwed M. Marczak A. Application of nanoparticles for magnetic hyperthermia for cancer treatment—the current state of knowledge. Cancers 2024 16 6 1156 10.3390/cancers16061156 38539491
    [Google Scholar]
  32. Peng J. Jing X. Wu J. Hong D. Hu X. Wang Q. Hu H. Cai X. Metformin’s effects on apoptosis of esophageal carcinoma cells and normal esophageal epithelial cells: An in vitro comparative study. BioMed Res. Int. 2020 2020 1 10 10.1155/2020/1068671 32258099
    [Google Scholar]
  33. Sinha K. Das J. Pal P.B. Sil P.C. Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch. Toxicol. 2013 87 7 1157 1180 10.1007/s00204‑013‑1034‑4 23543009
    [Google Scholar]
  34. Das J. Singh T.A. Lalruatsangi R. Sil P.C. Synthesis of nanohybrid consisting of taurine derived carbon dots and nanoceria for anticancer applications. Toxicol. Rep. 2024 13 101794 10.1016/j.toxrep.2024.101794 39554612
    [Google Scholar]
  35. Zhu S. Su L. Zhuang M. Liu L. Ji M. Liu J. Dai C. Xiao J. Guan Y. Yang L. Pu H. NEFL modulates nrn1-mediated mitochondrial pathway to promote diacetylmorphine-induced neuronal apoptosis. Mol. Neurobiol. 2024 10.1007/s12035‑024‑04629‑z 39557800
    [Google Scholar]
  36. Kaufmann S.H. Earnshaw W.C. Induction of apoptosis by cancer chemotherapy. Exp. Cell Res. 2000 256 1 42 49 10.1006/excr.2000.4838 10739650
    [Google Scholar]
  37. Green D.R. Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004 305 5684 626 629 10.1126/science.1099320 15286356
    [Google Scholar]
  38. Udumula M.P. Rashid F. Singh H. Pardee T. Luther S. Bhardwaj T. Anjaly K. Piloni S. Hijaz M. Gogoi R. Philip P.A. Munkarah A.R. Giri S. Rattan R. Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors. J. Ovarian Res. 2024 17 1 226 10.1186/s13048‑024‑01546‑6 39543742
    [Google Scholar]
  39. Khaliulin I. Hamoudi W. Amal H. The multifaceted role of mitochondria in autism spectrum disorder. Mol. Psychiatry 2024 10.1038/s41380‑024‑02725‑z 39223276
    [Google Scholar]
  40. Şen B. Kalhan H.K. Demir V. Güler E.E. Kayalı H.A. Subaşı E. Crystal structures, spectroscopic properties of new cobalt(II), nickel(II), zinc(II) and palladium(II) complexes derived from 2-acetyl-5-chloro thiophene thiosemicarbazone: Anticancer evaluation. Mater. Sci. Eng. C 2019 98 550 559 10.1016/j.msec.2018.12.080 30813058
    [Google Scholar]
  41. Kokina T.E. Glinskaya L.A. Sheludyakova L.A. Eremina Y.A. Klyushova L.S. Komarov V.Y. Piryazev D.A. Tkachev A.V. Larionov S.V. Synthesis, structure, and cytotoxicity of complexes of zinc(II), palladium(II), and copper(I) chlorides with (−)-camphor thiosemicarbazone. Polyhedron 2019 163 121 130 10.1016/j.poly.2019.02.020
    [Google Scholar]
  42. Obeng E. Apoptosis (programmed cell death) and its signals - A review. Braz. J. Biol. 2021 81 4 1133 1143 10.1590/1519‑6984.228437 33111928
    [Google Scholar]
  43. Jiang M. Li C. Mao C. Yu H. Zhou Y. Pu S. Li R. Liao Y. Zhang D. Yang P. Li M. Li M. The MAPK/ERK signaling pathway involved in Raddeanin A induces apoptosis via the mitochondrial pathway and G2 phase arrest in multiple myeloma. Sci. Rep. 2024 14 1 29061 10.1038/s41598‑024‑76465‑z 39580496
    [Google Scholar]
  44. Abate M. Festa A. Falco M. Lombardi A. Luce A. Grimaldi A. Zappavigna S. Sperlongano P. Irace C. Caraglia M. Misso G. Mitochondria as playmakers of apoptosis, autophagy and senescence. Semin. Cell Dev. Biol. 2020 98 139 153 10.1016/j.semcdb.2019.05.022 31154010
    [Google Scholar]
  45. Aggarwal R. Kumar P. Kumar S. Sadana R. Lwanga R. Campbell J. Chaubal V. Design, synthesis, and in vitro cytotoxic studies of some novel arylidene-hydrazinyl-thiazoles as anticancer and apoptosis-inducing agents. ACS Omega 2024 9 37 38832 38845 10.1021/acsomega.4c04924 39310139
    [Google Scholar]
  46. Liu Y. Sun Q. Du K. Long H. Zhang D. Zheng J. Zhao Y. Zhang H. External pressure induces the dysfunction of spermatogonia via triggering the intrinsic pathway of apoptosis. Transl. Androl. Urol. 2024 13 8 1405 1415 10.21037/tau‑24‑158 39280678
    [Google Scholar]
  47. Bhuker S. Kaur A. Rajauria K. Tuli H.S. Saini A.K. Saini R.V. Gupta M. Allicin: A promising modulator of apoptosis and survival signaling in cancer. Med. Oncol. 2024 41 9 210 10.1007/s12032‑024‑02459‑6 39060753
    [Google Scholar]
  48. Köpf-Maier P. Klapötke T. Antitumor activity of some organomettalic bismuth(III)thiolates. Inorg. Chim. Acta 1988 152 1 49 52 10.1016/S0020‑1693(00)90730‑8
    [Google Scholar]
  49. Kondo Y. Satoh M. Imura N. Akimoto M. Effect of bismuth nitrate given in combination withcis-diamminedichloroplatinum(II) on the antitumor activity and renal toxicity of the latter in nude mice inoculated with human bladder tumor. Cancer Chemother. Pharmacol. 1991 29 1 19 23 10.1007/BF00686330 1742844
    [Google Scholar]
  50. Jansson P.J. Sharpe P.C. Bernhardt P.V. Richardson D.R. Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: identification of pronounced redox activity and characterization of their antitumor activity. J. Med. Chem. 2010 53 15 5759 5769 10.1021/jm100561b 20597487
    [Google Scholar]
  51. Redza-Dutordoir M. Averill-Bates D.A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta Mol. Cell Res. 2016 1863 12 2977 2992 10.1016/j.bbamcr.2016.09.012 27646922
    [Google Scholar]
  52. Luo Y. Liu R. Zhang H. Wang H. Yin H. Tian G. Wang B. Yan Y. Ding Z. Dai J. Niu L. Yuan G. Pan Y. Amantadine against glioma via ROS-mediated apoptosis and autophagy arrest. Cell Death Dis. 2024 15 11 834 10.1038/s41419‑024‑07228‑x 39548081
    [Google Scholar]
  53. Xie J. Yuan C. Yang S. Ma Z. Li W. Mao L. Jiao P. Liu W. The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death. Cell. Mol. Biol. Lett. 2024 29 1 138 10.1186/s11658‑024‑00659‑6 39516736
    [Google Scholar]
  54. Wu S. Ding D. Wang D. Regulated cell death pathways in pathological cardiac hypertrophy. Rev. Cardiovasc. Med. 2024 25 10 366 10.31083/j.rcm2510366 39484135
    [Google Scholar]
  55. Mesquita F.P. de Oliveira F.L. da Silva E.L. Brito D.M.S. de Moraes M.E.A. Souza P.F.N. Montenegro R.C. Synthetic peptides induce human colorectal cancer cell death via proapoptotic pathways. ACS Omega 2024 9 42 43252 43263 10.1021/acsomega.4c08194 39464451
    [Google Scholar]
  56. Flynn J.M. Melov S. SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic. Biol. Med. 2013 62 4 12 10.1016/j.freeradbiomed.2013.05.027 23727323
    [Google Scholar]
  57. Gogna T. Housden B.E. Houldsworth A. Exploring the role of reactive oxygen species in the pathogenesis and pathophysiology of alzheimer’s and parkinson’s disease and the efficacy of antioxidant treatment. Antioxidants 2024 13 9 1138 10.3390/antiox13091138 39334797
    [Google Scholar]
  58. Sun X. Wu S. Mao C. Qu Y. Xu Z. Xie Y. Jiang D. Song Y. Therapeutic potential of hydrogen sulfide in ischemia and reperfusion injury. Biomolecules 2024 14 7 740 10.3390/biom14070740 39062455
    [Google Scholar]
  59. Oyama T. Yamamoto T. Kameda T. Kamiya T. Abe H. Abe T. Tanuma S. Supplementation of nicotinic acid and its derivatives up-regulates cellular NAD+ level rather than nicotinamide derivatives in cultured normal human epidermal keratinocytes. Life 2024 14 3 413 10.3390/life14030413 38541737
    [Google Scholar]
  60. Houldsworth A. Role of oxidative stress in neurodegenerative disorders: A review of reactive oxygen species and prevention by antioxidants. Brain Commun. 2023 6 1 fcad356 10.1093/braincomms/fcad356 38214013
    [Google Scholar]
  61. Chen H.H. Chen Y.T. Huang Y.W. Tsai H.J. Kuo C.C. 4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling. Free Radic. Biol. Med. 2012 52 6 1054 1066 10.1016/j.freeradbiomed.2011.12.012 22245092
    [Google Scholar]
  62. Finley L.W.S. Carracedo A. Lee J. Souza A. Egia A. Zhang J. Teruya-Feldstein J. Moreira P.I. Cardoso S.M. Clish C.B. Pandolfi P.P. Haigis M.C. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell 2011 19 3 416 428 10.1016/j.ccr.2011.02.014 21397863
    [Google Scholar]
  63. Bell E.L. Emerling B.M. Ricoult S.J.H. Guarente L. SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production. Oncogene 2011 30 26 2986 2996 10.1038/onc.2011.37 21358671
    [Google Scholar]
  64. de Melo Silva A.J. de Melo Gama J.E. de Oliveira S.A. The role of Bcl‐2 family proteins and sorafenib resistance in hepatocellular carcinoma. Int. J. Cell Biol. 2024 2024 1 4972523 10.1155/2024/4972523 39188653
    [Google Scholar]
  65. Green D.R. Apoptotic pathways: Ten minutes to dead. Cell 2005 121 5 671 674 10.1016/j.cell.2005.05.019 15935754
    [Google Scholar]
  66. Al-Shajrawi O. Tarawneh I. Tengku Din T.A.D.A.A. Afolabi H. The role of microalgal extracts and their combination with tamoxifen in the modulation of breast cancer immunotherapy (Review). Mol. Clin. Oncol. 2024 22 1 6 10.3892/mco.2024.2801 39559458
    [Google Scholar]
  67. Ding Z. Liu C. Zhang Z. Zhang C. Huang F. Effect of mitochondrial calcium homeostasis-mediated endogenous enzyme activation on tenderness of beef muscle based on MCU modulators. Food Chem. X 2024 22 101366 10.1016/j.fochx.2024.101366 38623508
    [Google Scholar]
  68. Guo Y. Zhu L. Duan Y. Hu Y. Li L. Fan W. Song F. Cai Y. Liu Y. Zheng G. Ge M. Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission. Cell Death Dis. 2024 15 2 125 10.1038/s41419‑024‑06511‑1 38336839
    [Google Scholar]
  69. Liu C. Ding Z. Zhang Z. Zhao L. Zhang C. Huang F. Morphological changes of mitochondria-related to apoptosis during postmortem aging of beef muscles. Food Chem. X 2023 19 100806 10.1016/j.fochx.2023.100806 37780314
    [Google Scholar]
  70. Qi F. Inagaki Y. Gao B. Cui X. Xu H. Kokudo N. Li A. Tang W. Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas‐ and mitochondria‐mediated pathways. Cancer Sci. 2011 102 5 951 958 10.1111/j.1349‑7006.2011.01900.x 21288283
    [Google Scholar]
  71. Liao Y. Wei F. He Z. He J. Ai Y. Guo C. Zhou L. Luo D. Li C. Wen Y. Zeng J. Ma X. Animal-derived natural products for hepatocellular carcinoma therapy: Current evidence and future perspectives. Front. Pharmacol. 2024 15 1399882 10.3389/fphar.2024.1399882 38803433
    [Google Scholar]
  72. Jia J. Li J. Zheng Q. Li D. A research update on the antitumor effects of active components of Chinese medicine ChanSu. Front. Oncol. 2022 12 1014637 10.3389/fonc.2022.1014637 36237327
    [Google Scholar]
  73. El-Seedi H.R. Yosri N. El-Aarag B. Mahmoud S.H. Zayed A. Du M. Saeed A. Musharraf S.G. El-Garawani I.M. Habib M.R. Tahir H.E. Hegab M.M. Zou X. Guo Z. Efferth T. Khalifa S.A.M. Chemistry and the potential antiviral, anticancer, and anti-inflammatory activities of cardiotonic steroids derived from toads. Molecules 2022 27 19 6586 10.3390/molecules27196586 36235123
    [Google Scholar]
  74. Kuo J.Y. Liao C.L. Ma Y.S. Kuo C.L. Chen J.C. Huang Y.P. Huang W.W. Peng S.F. Chung J.G. Combination treatment of sorafenib and bufalin induces apoptosis in NCI-H292 human lung cancer cells in vitro. In Vivo 2022 36 2 582 595 10.21873/invivo.12741 35241510
    [Google Scholar]
  75. Bai Y. Wang X. Cai M. Ma C. Xiang Y. Hu W. Zhou B. Zhao C. Dai X. Li X. Zhao H. Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition. Am. J. Cancer Res. 2021 11 1 200 214 33520369
    [Google Scholar]
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