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Anti-tumor Activity and Apoptosis-regulation Mechanisms of Bufalin in Various Cancers: New Hope for Cancer Patients

  • Yin, Pei-Hao (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Liu, Xuan (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Qiu, Yan-Yan (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Cai, Jian-Feng (Department of Chemistry, University of South Florida) ;
  • Qin, Jian-Min (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Zhu, Hui-Rong (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Li, Qi (Department of General Surgery and Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine)
  • 발행 : 2012.11.30

초록

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

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참고문헌

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피인용 문헌

  1. MicroRNA-497 and bufalin act synergistically to inhibit colorectal cancer metastasis vol.35, pp.3, 2014, https://doi.org/10.1007/s13277-013-1342-6
  2. Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway vol.13, pp.1, 2015, https://doi.org/10.3892/mmr.2015.4583
  3. Bufalin Induces Mitochondrial Pathway-Mediated Apoptosis in Lung Adenocarcinoma Cells vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10495
  4. ABL-N may induce apoptosis of human prostate cancer cells through suppression of KLF5, ICAM-1 and Stat5b, and upregulation of Bax/Bcl-2 ratio: An in vitro and in vivo study vol.34, pp.6, 2015, https://doi.org/10.3892/or.2015.4293
  5. Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors vol.36, pp.3, 2015, https://doi.org/10.3892/ijmm.2015.2268
  6. The effect and mechanism of bufalin on regulating hepatocellular carcinoma cell invasion and metastasis via Wnt/β-catenin signaling pathway vol.48, pp.1, 2015, https://doi.org/10.3892/ijo.2015.3250
  7. Antitumor action of the peroxisome proliferator‑activated receptor‑γ agonist rosiglitazone in hepatocellular carcinoma pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3554
  8. Bufalin suppresses cancer stem-like cells in gemcitabine-resistant pancreatic cancer cells via Hedgehog signaling vol.14, pp.3, 2016, https://doi.org/10.3892/mmr.2016.5471
  9. miR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cells vol.27, pp.1, 2016, https://doi.org/10.1097/CAD.0000000000000296
  10. Effects of active bufadienolide compounds on human cancer cells and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells vol.36, pp.3, 2016, https://doi.org/10.3892/or.2016.4946
  11. The effects of bufadienolides on HER2 overexpressing breast cancer cells vol.37, pp.6, 2016, https://doi.org/10.1007/s13277-015-4381-3
  12. Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly vol.37, pp.7, 2016, https://doi.org/10.1038/aps.2016.30
  13. Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes vol.12, pp.1, 2017, https://doi.org/10.1186/s11671-017-2346-8
  14. Blocking autophagy enhances the pro-apoptotic effect of bufalin on human gastric cancer cells through endoplasmic reticulum stress vol.6, pp.10, 2017, https://doi.org/10.1242/bio.026344
  15. Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation pp.0974-0449, 2017, https://doi.org/10.1007/s12288-017-0883-z
  16. Phytochemical based nanomedicines against cancer: current status and future prospects pp.1029-2330, 2017, https://doi.org/10.1080/1061186X.2017.1408115
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  18. Cancer Stem Cells: The Potential Targets of Chinese Medicines and Their Active Compounds vol.17, pp.6, 2016, https://doi.org/10.3390/ijms17060893
  19. Effect of matrine combined with cisplatin on the expression of XIAP in human rhabdomyosarcoma RD cells vol.12, pp.5, 2016, https://doi.org/10.3892/ol.2016.5150
  20. Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis vol.14, pp.1, 2017, https://doi.org/10.3892/ol.2017.6223
  21. Hyperthermia and radiation reduce the toxic side-effects of bufadienolides for cancer therapy vol.14, pp.1, 2017, https://doi.org/10.3892/ol.2017.6256
  22. Bufalin reverses acquired drug resistance by inhibiting stemness in colorectal cancer cells vol.38, pp.3, 2017, https://doi.org/10.3892/or.2017.5826
  23. Effects of bufalin on the mTOR/p70S6K pathway and apoptosis in esophageal squamous cell carcinoma in nude mice vol.40, pp.2, 2017, https://doi.org/10.3892/ijmm.2017.3039
  24. Bufalin induced apoptosis in SCC-4 human tongue cancer cells by decreasing Bcl-2 and increasing Bax expression via the mitochondria-dependent pathway vol.16, pp.6, 2017, https://doi.org/10.3892/mmr.2017.7651
  25. Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides vol.19, pp.9, 2018, https://doi.org/10.3390/ijms19092769
  26. The Development of Toad Toxins as Potential Therapeutic Agents vol.10, pp.8, 2018, https://doi.org/10.3390/toxins10080336