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Low-level laser selectively inhibiting colorectal cancer cell metabolic activity and inducing apoptosis for delaying the development of intestinal cancer

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Abstract

Low-level laser irradiation (LLLI) is a novel approach that shows promise for the treatment of colorectal cancer (CRC). However, the molecular mechanisms underlying its biochemical effects and gene expression remain unclear. Here, LLLI (632.8 nm) was used to treat CRC RKO cells and normal small intestinal NCM460 cells. LLLI showed a significant dose- and time-dependent effect on cell viability, in which a single dose of irradiation at 15 J/cm2 selectively inhibited the growth of RKO cells but largely unaffected the activity of NCM460 cells. And then, LLLI produced an internal response, effectively reducing the level of H2O2 in tumor cells, downregulating the mitochondrial membrane potential, and improving the efficiency of apoptosis in CRC, but no internal response was observed in NCM460 cells under the same conditions. Furthermore, the expression of several important genes in the classical WNT pathway was significantly downregulated, and the pathway was inactivated after LLLI intervention, thereby inhibiting tumor cell growth. Simultaneously, TNF-α was effectively activated to stimulate the caspase family members of the death effector to initiate apoptosis led by the extrinsic pathway. LLLI successfully achieves tumor cell normalization while delivering a potent anticancer effect, expected to be a novel therapeutic modality for CRC.

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References

  1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71, 209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Brouwer, N. P. M., Bos, A., Lemmens, V., Tanis, P. J., Hugen, N., Nagtegaal, I. D., et al. (2018). An overview of 25 years of incidence, treatment and outcome of colorectal cancer patients. International Journal of Cancer, 143, 2758–2766. https://doi.org/10.1002/ijc.31785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nurgali, K., Jagoe, R. T., & Abalo, R. (2018). Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Frontiers in Pharmacology, 9, 245. https://doi.org/10.3389/fphar.2018.00245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schell, M. J., Yang, M., Teer, J. K., Lo, F. Y., Madan, A., Coppola, D., et al. (2016). A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC. Nature Communications, 7, 11743. https://doi.org/10.1038/ncomms11743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Li, Q., Sun, B., Liu, Z., Cheng, R., Li, Y., & Zhao, X. (2014). Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression. Journal of Experimental & Clinical Cancer Research, 33, 107. https://doi.org/10.1186/s13046-014-0107-4

    Article  CAS  Google Scholar 

  6. Chan, J. S., Tan, M. J., Sng, M. K., Teo, Z., Phua, T., Choo, C. C., et al. (2017). Cancer-associated fibroblasts enact field cancerization by promoting extratumoral oxidative stress. Cell Death & Disease, 8, e2562. https://doi.org/10.1038/cddis.2016.492

    Article  CAS  Google Scholar 

  7. Cho, Y. H., Ro, E. J., Yoon, J. S., Mizutani, T., Kang, D. W., Park, J. C., et al. (2020). 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/beta-catenin pathway activation. Nature Communications, 11, 5321. https://doi.org/10.1038/s41467-020-19173-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liang, W. Z., Liu, P. F., Fu, E., Chung, H. S., Jan, C. R., Wu, C. H., et al. (2015). Selective cytotoxic effects of low-power laser irradiation on human oral cancer cells. Lasers in Surgery and Medicine, 47, 756–764. https://doi.org/10.1002/lsm.22419

    Article  PubMed  Google Scholar 

  9. Xia, Y., Yu, W., Cheng, F., Rao, T., Ruan, Y., Yuan, R., et al. (2021). Photobiomodulation with blue laser inhibits bladder cancer progression. Frontiers in Oncology, 11, 701122. https://doi.org/10.3389/fonc.2021.701122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. de Pauli, P. M., Araújo, A. L. D., Arboleda, L. P. A., Palmier, N. R., Fonsêca, J. M., Gomes-Silva, W., et al. (2019). Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review. Oral Oncology, 93, 21–28. https://doi.org/10.1016/j.oraloncology.2019.04.004

    Article  CAS  Google Scholar 

  11. Calabrese, E. J., Bachmann, K. A., Bailer, A. J., Bolger, P. M., Borak, J., Cai, L., et al. (2007). Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicology and Applied Pharmacology, 222, 122–128. https://doi.org/10.1016/j.taap.2007.02.015

    Article  CAS  PubMed  Google Scholar 

  12. Calabrese, E. J. (2018). Hormesis: path and progression to significance. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms19102871

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kitazawa, M., Hatta, T., Sasaki, Y., Fukui, K., Ogawa, K., Fukuda, E., et al. (2020). Promotion of the Warburg effect is associated with poor benefit from adjuvant chemotherapy in colorectal cancer. Cancer Science, 111, 658–666. https://doi.org/10.1111/cas.14275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yang, X., Liu, T. C., Liu, S., Zhu, W., Li, H., Liang, P., et al. (2020). Promoted viability and differentiated phenotype of cultured chondrocytes with low level laser irradiation potentiate efficacious cells for therapeutics. Frontiers in Bioengineering and Biotechnology, 8, 468. https://doi.org/10.3389/fbioe.2020.00468

    Article  PubMed  PubMed Central  Google Scholar 

  15. Khori, V., Alizadeh, A. M., Gheisary, Z., Farsinejad, S., Najafi, F., Khalighfard, S., et al. (2016). The effects of low-level laser irradiation on breast tumor in mice and the expression of Let-7a, miR-155, miR-21, miR125, and miR376b. Lasers in Medical Science, 31, 1775–1782. https://doi.org/10.1007/s10103-016-2049-x

    Article  PubMed  Google Scholar 

  16. Tian, Y., Lee, Y., Kim, H., & Kang, H. W. (2020). In vitro anti-tumor effect of low-power laser irradiation (LPLI) on gastroenterological carcinoma cells. Lasers in Medical Science, 35, 677–685. https://doi.org/10.1007/s10103-019-02869-3

    Article  PubMed  Google Scholar 

  17. Tian, Y., Kim, H., & Kang, H. W. (2021). In vitro anti-tumor effect of high-fluence low-power laser light on apoptosis of human colorectal cancer cells. Lasers in Medical Science, 36, 513–520. https://doi.org/10.1007/s10103-020-03050-x

    Article  PubMed  Google Scholar 

  18. Yang, X., Liu, S., Li, S., Wang, P., Zhu, W., Liang, P., et al. (2017). Salvianolic acid B regulates gene expression and promotes cell viability in chondrocytes. Journal of Cellular and Molecular Medicine, 21, 1835–1847. https://doi.org/10.1111/jcmm.13104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Osterman, E., & Glimelius, B. (2018). Recurrence risk after up-to-date colon cancer staging, surgery, and pathology: analysis of the entire Swedish population. Diseases of the Colon and Rectum, 61, 1016–1025. https://doi.org/10.1097/DCR.0000000000001158

    Article  PubMed  Google Scholar 

  20. Wang, F., Chen, T. S., Xing, D., Wang, J. J., & Wu, Y. X. (2005). Measuring dynamics of caspase-3 activity in living cells using FRET technique during apoptosis induced by high fluence low-power laser irradiation. Lasers in Surgery and Medicine, 36, 2–7. https://doi.org/10.1002/lsm.20130

    Article  PubMed  Google Scholar 

  21. Sies, H., & Jones, D. P. (2020). Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nature Reviews Molecular Cell Biology, 21, 363–383. https://doi.org/10.1038/s41580-020-0230-3

    Article  CAS  PubMed  Google Scholar 

  22. Haidar, M., Metheni, M., Batteux, F., & Langsley, G. (2019). TGF-beta2, catalase activity, H2O2 output and metastatic potential of diverse types of tumour. Free Radical Biology & Medicine, 134, 282–287. https://doi.org/10.1016/j.freeradbiomed.2019.01.010

    Article  CAS  Google Scholar 

  23. Simon, H.-U., Haj-Yehia, A., & Levi-Schaffer, F. (2000). Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5, 415–8. https://doi.org/10.1023/a:1009616228304

    Article  CAS  PubMed  Google Scholar 

  24. Redza-Dutordoir, M., & Averill-Bates, D. A. (2016). Activation of apoptosis signaling pathways by reactive oxygen species. Biochimica et Biophysica Acta, 1863, 2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012

    Article  CAS  PubMed  Google Scholar 

  25. Nusse, R., & Clevers, H. (2017). Wnt/beta-Catenin signaling, disease, and emerging therapeutic modalities. Cell, 169, 985–999. https://doi.org/10.1016/j.cell.2017.05.016

    Article  CAS  PubMed  Google Scholar 

  26. Nie, X., Xia, F., Liu, Y., Zhou, Y., Ye, W., Hean, P., et al. (2019). Downregulation of Wnt3 suppresses colorectal cancer development through inhibiting cell proliferation and migration. Frontiers in Pharmacology, 10, 1110. https://doi.org/10.3389/fphar.2019.01110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li, G., Su, Q., Liu, H., Wang, D., Zhang, W., Lu, Z., et al. (2018). Frizzled7 promotes epithelial-to-mesenchymal transition and stemness via activating canonical Wnt/beta-catenin pathway in gastric cancer. International Journal of Biological Sciences, 14, 280–293. https://doi.org/10.7150/ijbs.23756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bagheri, H. S., Mousavi, M., Rezabakhsh, A., Rezaie, J., Rasta, S. H., Nourazarian, A., et al. (2018). Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling. Lasers in Medical Science, 33, 1131–1145. https://doi.org/10.1007/s10103-018-2495-8

    Article  PubMed  Google Scholar 

  29. Zhang, X., Shang, W., Yuan, J., Hu, Z., Peng, H., Zhu, J., et al. (2016). Positive feedback cycle of TNFalpha promotes staphylococcal enterotoxin B-Induced THP-1 cell apoptosis. Frontiers in Cellular and Infection Microbiology, 6, 109. https://doi.org/10.3389/fcimb.2016.00109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jiang, Y., Yu, M., Hu, X., Han, L., Yang, K., Ba, H., et al. (2017). STAT1 mediates transmembrane TNF-alpha-induced formation of death-inducing signaling complex and apoptotic signaling via TNFR1. Cell Death and Differentiation, 24, 660–671. https://doi.org/10.1038/cdd.2016.162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang, Z., Ao, X., Shen, Z., Ao, L., Wu, X., Pu, C., et al. (2021). TNF-alpha augments CXCL10/CXCR3 axis activity to induce epithelial-mesenchymal transition in colon cancer cell. International Journal of Biological Sciences, 17, 2683–2702. https://doi.org/10.7150/ijbs.61350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Borovski, T., Vellinga, T. T., Laoukili, J., Santo, E. E., Fatrai, S., van Schelven, S., et al. (2017). Inhibition of RAF1 kinase activity restores apicobasal polarity and impairs tumour growth in human colorectal cancer. Gut, 66, 1106–1115. https://doi.org/10.1136/gutjnl-2016-311547

    Article  CAS  PubMed  Google Scholar 

  33. Hatzivassiliou, G., Haling, J. R., Chen, H., Song, K., Price, S., Heald, R., et al. (2013). Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature, 501, 232–236. https://doi.org/10.1038/nature12441

    Article  CAS  PubMed  Google Scholar 

  34. Ishii, N., Harada, N., Joseph, E. W., Ohara, K., Miura, T., Sakamoto, H., et al. (2013). Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Research, 73, 4050–4060. https://doi.org/10.1158/0008-5472.CAN-12-3937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Plemel, J. R., Caprariello, A. V., Keough, M. B., Henry, T. J., Tsutsui, S., Chu, T. H., et al. (2017). Unique spectral signatures of the nucleic acid dye acridine orange can distinguish cell death by apoptosis and necroptosis. Journal of Cell Biology, 216, 1163–1181. https://doi.org/10.1083/jcb.201602028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Damas-Souza, D. M., Nunes, R., & Carvalho, H. F. (2019). An improved acridine orange staining of DNA/RNA. Acta Histochemica, 121, 450–454. https://doi.org/10.1016/j.acthis.2019.03.010

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Guangzhou Municipal Science and Technology Project (Grant Number: 202102010110), Guangzhou Municipal Health Commission Project (Grant Number: 20211A011023), and Guangdong Pharmaceutical Association Project (Grant Number: 2022MZ12).

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  1. Shaojie Liu and Qiguang Zhong have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China

    Shaojie Liu, Qiguang Zhong, Hanshuo Zhang, Jingqing Ren & Lihua Zhang

  2. Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China

    Weicong Zhu, Shuliang Cui & Xiaohong Yang

  3. School of BioSciences, University of Melboume, Victoria, Australia

    Shuliang Cui

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  1. Shaojie Liu
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Contributions

SL: conceptualization, project administration, investigation, funding acquisition, supervision, writing—original draft. QZ: investigation, validation, visualization, formal analysis, writing—original draft. WZ: formal analysis, funding acquisition, investigation. HZ: data curation. JR: methodology. LZ: software. SC: formal analysis, writing—review and editing. XY: conceptualization, project administration, resources, funding acquisition, writing—review and editing.

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Correspondence to Shaojie Liu or Xiaohong Yang.

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Liu, S., Zhong, Q., Zhu, W. et al. Low-level laser selectively inhibiting colorectal cancer cell metabolic activity and inducing apoptosis for delaying the development of intestinal cancer. Photochem Photobiol Sci 22, 1707–1720 (2023). https://doi.org/10.1007/s43630-023-00409-1

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