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Bcl-2 Interacts with Beclin 1 and Regulates Autophagy in 7, 12-Dimethylbenz[a]anthracene-Induced Hamster Buccal-Pouch Squamous-Cell Tumorigenesis

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Abstract

Objective

Autophagy is a programmed cell death procedure, which has essential functions in tumorigenesis. However, its temporal expression and function under different status are yet to be determined. This study aims to investigate the temporal expression of autophagy and its possible function in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch cancer model (HBPCM).

Methods

A total of 50 hamster buccal-pouch tumorigenesis models were established by painting DMBA for 4, 8, 10 and 13 weeks. The expression and subcellular localization of LC3, Beclin 1 and Bcl-2 in buccal lesions were evaluated by immunohistochemical staining and Western blotting. DNA damage was observed by immunohistochemical staining of 8-oHdG. The relationship between Beclin 1 and Bcl-2 was analyzed by immunofluorescence colocalization.

Results

The expression levels of LC3 and Beclin 1 associated with autophagy in the experimental buccal pouch of HBPCM were significantly upregulated after 4 weeks (P<0.05), but gradually downregulated after 13 weeks of HBPCM induction. By contrast, the expression level of Bcl-2 was significantly upregulated after 13 weeks. The co-localized regions of Bcl-2 and Beclin 1 peaked after 4 weeks and then decreased gradually. The DNA damage in epithelial cells increased slightly after 4 weeks, and then rapidly decreased over the next 2 months.

Conclusion

Autophagy is motivated by a tumor suppressor that diminishes carcinogen-induced DNA damage. However, autophagy is gradually suppressed, which may be attributed to the interaction between Bcl-2 and Beclin 1. This result indicates that the promotion of autophagy may suppress malignant transformation and provide new insights on future potential treatments of HBPCM.

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References

  1. Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin, 2002,52(4):195–215

    Article  PubMed  Google Scholar 

  2. Rivera C, Gallegos R, Figueroa C. Biomarkers of progression to oral cancer in patients with dysplasia: A systematic review. Mol Clin Oncol, 2020,13(5):42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu Q, Wang J, Wang B, et al. Paper based plasmonic platform for sensitive, noninvasive, and rapid cancer screening. Biosens Bioelectron, 2014,15(54):128–134

    Article  Google Scholar 

  4. Gong C, Bauvy C, Tonelli G, et al. Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Oncogene, 2013, 32(18):2261–2272

    Article  CAS  PubMed  Google Scholar 

  5. Chen N, Debnath J. Autophagy and tumorigenesis. FEBS Lett, 2010,584(7):1427–1435

    Article  CAS  PubMed  Google Scholar 

  6. Liu K, Lee J, Kim JY, et al. Mitophagy controls the activities of tumor suppressor p53 to regulate hepatic cancer stem cells. Mol Cell, 2017,68(2):281–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Scherz-Shouval R, Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci, 2011,36(1):30–38

    Article  CAS  PubMed  Google Scholar 

  8. Liu K, Lee J, Ou JHJ. Autophagy and mitophagy in hepatocarcinogenesis. Mol Cell Oncol, 2018,5(2): e1405142

    Article  PubMed  PubMed Central  Google Scholar 

  9. Das CK, Mandal M, Kögel D. Pro-survival autophagy and cancer cell resistance to therapy. Cancer Metastasis Rev, 2018,37(4):749–766

    Article  CAS  PubMed  Google Scholar 

  10. Zou YM, Hu GY, Zhao XQ, et al. Hypoxia-induced autophagy contributes to radioresistance via c-Jun-mediated Beclin1 expression in lung cancer cells. J Huazhong Univ Sci Technolog Med Sci, 2014,34(5):761–767

    Article  CAS  PubMed  Google Scholar 

  11. He C, Levine B. The Beclin 1 interactome. Curr Opin Cell Biol, 2010,22(2):140–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Marquez RT, Xu L. Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res, 2012,2(2):214–221

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wu SY, Lan SH, Cheng DE, et al. Ras-related tumorigenesis is suppressed by BNIP3-mediated autophagy through inhibition of cell proliferation. Neoplasia, 2011,13(12):1171–1182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. van der Heijden M, Winton DJ, Wermeulen L. Turning off the BCL-2 switch to prevent intestinal tumorigenesis. Oncotarget, 2016,7(20):28763–28764

    Article  PubMed  PubMed Central  Google Scholar 

  15. Eveson JW, MacDonald DG. Quantitative histological changes during early experimental carcinogenesis in the hamster cheek pouch. Br J Dermatol, 1978,98(6):639–644

    Article  CAS  PubMed  Google Scholar 

  16. Klaunig JE, Wang Z, Pu X, et al. Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol, 2011,254(2):86–99

    Article  CAS  PubMed  Google Scholar 

  17. Chen YK, Yang SH, Huang AH, et al. Aberrant expression in multiple components of the transforming growth factor-beta1-induced Smad signaling pathway during 7,12-dimethylbenz[a]anthracene-induced hamster buccal-pouch squamous-cell carcinogenesis. Oral Oncol, 2011,47(4):262–267

    Article  CAS  PubMed  Google Scholar 

  18. Tam NN, Nyska A, Maronpot RR, et al. Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants. Prostate, 2006,66(1):57–69

    Article  CAS  PubMed  Google Scholar 

  19. Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta, 2009,1793(9):1516–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhou S, Zhao L, Kuang M, et al. Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde? Cancer Lett, 2012,323(2):115–127

    Article  CAS  PubMed  Google Scholar 

  21. Yoshioka A, Miyata H, Doki Y, et al. LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers. Int J Oncol, 2008,33(3):461–468

    CAS  PubMed  Google Scholar 

  22. Wu JS, Li L, Wang SS, et al. Autophagy is positively associated with the accumulation of myeloid-derived suppressor cells in 4-nitroquinoline-1-oxide-induced oral cancer. Oncology reports, 2018,40(6):3381–3391

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Nagini S. Of humans and hamsters: the hamster buccal pouch carcinogenesis model as a paradigm for oral oncogenesis and chemoprevention. Anticancer Agents Med Chem, 2009,9(8):843–852

    Article  CAS  PubMed  Google Scholar 

  24. Koneri K, Goi T, Hirono Y, et al. Beclin 1 gene inhibits tumor growth in colon cancer cell lines. Anticancer Res, 2007,27(3B):1453–1457

    CAS  PubMed  Google Scholar 

  25. Marino ML, Pellegrini P, Di Lernia G, et al. Autophagy is a protective mechanism for human melanoma cells under acidic stress. J Biol Chem, 2012,287(36):30 664–30 676

    Article  CAS  Google Scholar 

  26. He C, Bassik MC, Moresi V, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature, 2012,481(7382):511–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 2005,122(6):927–939

    Article  CAS  PubMed  Google Scholar 

  28. Moon SM, Ahn MY, Kwon SM, et al. Homeobox C5 expression is associated with the progression of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. J Oral Pathol Med, 2012,41(6):470–476

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. The authors contributed eqaully to this work.

Authors and Affiliations

  1. Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China

    Qian Liu, Yang Liu, Shu-e Li & Jin-huan Geng

Authors
  1. Qian Liu
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  2. Yang Liu
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  3. Shu-e Li
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  4. Jin-huan Geng
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Correspondence to Qian Liu.

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The authors have no conflict of interest.

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Liu, Q., Liu, Y., Li, Se. et al. Bcl-2 Interacts with Beclin 1 and Regulates Autophagy in 7, 12-Dimethylbenz[a]anthracene-Induced Hamster Buccal-Pouch Squamous-Cell Tumorigenesis. CURR MED SCI 41, 1198–1204 (2021). https://doi.org/10.1007/s11596-021-2472-5

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  • DOI: https://doi.org/10.1007/s11596-021-2472-5

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