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Effect of pre-low-dose irradiation on anticancer activities of gallic acid in leukemic K562 and K562/Dox cells: cell viability and cellular energetic state studies

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Abstract

The aim of this study was to determine the effects of pre-low-dose irradiation followed by gallic acid (GA) on cell viability and cellular energetic state of leukemic K562 and K562/Dox cells. The cells were irradiated with 0.02, 0.05, and 0.1 Gy of X-rays. For determining cell viability, pre-low-dose irradiation was followed by 10 or 100 µM GA at 24 h post-irradiation, and the cell viability was then determined at 48 h post-irradiation. For cellular energetic state, pre-low-dose irradiation was followed by 10 or 100 µM GA at 1.5 h post-irradiation and the mitochondrial activity, mitochondrial membrane potential (ΔΨm), and ATP level were determined at 3 h post-irradiation. The % cell viability was significantly decreased in both cells that were irradiated with X-rays followed by treatment with 10 or 100 µM GA at 24 h post-irradiation, when compared with control group. However, this did not happen when compared with GA alone without any pre-low-dose irradiation. The mitochondrial activity had significantly decreased in 10 µM GA-treated K562 cells and the mitochondrial activity, ΔΨm, and ATP levels had significantly decreased in 10 µM GA-treated K562/Dox cells after irradiation to X-rays when compared with GA alone group. In addition, the ΔΨm and ATP levels was significantly decreased in only 100 µM GA-treated K562/Dox cells, but was not decreased in 100 µM GA-treated K562 cells after exposure to X-rays. These findings suggest that pre-low-dose irradiation followed by GA could not kill K562 and K562/Dox cells, but could improve cellular energetic damage of GA effects possibly through mitochondrial impairment.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727–41. https://doi.org/10.1016/s0006-2952(98)00307-4.

    Article  PubMed  CAS  Google Scholar 

  3. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229. https://doi.org/10.1124/pr.56.2.6.

    Article  PubMed  CAS  Google Scholar 

  4. Meredith AM, Dass CR. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J Pharm Pharmacol. 2016;68(6):729–41. https://doi.org/10.1111/jphp.12539.

    Article  PubMed  CAS  Google Scholar 

  5. Miller AA, Salewski E. Prospects for pirarubicin. Med Pediatr Oncol. 1994;22(4):261–8. https://doi.org/10.1002/mpo.2950220410.

    Article  PubMed  CAS  Google Scholar 

  6. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. 4’-O-tetrahydropyranyladriamycin as a potential new antitumor agent. Cancer Res. 1982;42(4):1462–7.

    PubMed  CAS  Google Scholar 

  7. Kunimoto S, Miura K, Takahashi Y, Takeuchi T, Umezawa H. Rapid uptake by cultured tumor cells and intracellular behavior of 4’-O-tetrahydropyranyladriamycin. J Antibiot (Tokyo). 1983;36(3):312–7. https://doi.org/10.7164/antibiotics.36.312.

    Article  CAS  Google Scholar 

  8. Mizutani H, Hotta S, Nishimoto A, Ikemura K, Miyazawa D, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S. Pirarubicin, an anthracycline anticancer agent, induces apoptosis through generation of hydrogen peroxide. Anticancer Res. 2017;37(11):6063–9. https://doi.org/10.21873/anticanres.12054.

    Article  PubMed  CAS  Google Scholar 

  9. Lynch TJ, Adjei AA, Bunn PA Jr, DuBois RN, Gandara DR, Giaccone G, Govindan R, Herbst RS, Johnson BE, Khuri FR, Perez-Soler R, Rosell R, Rowinsky EK, Sandler AB, Scagliotti GV, Schiller JH, Shapiro GI, Socinski MA, Hart CS. Novel agents in the treatment of lung cancer: conference summary statement. Clin Cancer Res. 2004;10(12 Pt 2):4199s–204s. https://doi.org/10.1158/1078-0432.Ccr-040021.

    Article  PubMed  Google Scholar 

  10. Johnson DH, Schiller JH. Novel therapies for the treatment of non-small cell lung cancer. Cancer Chemother Biol Response Modif. 2002;20:763–86.

    PubMed  CAS  Google Scholar 

  11. Maurya DK, Nandakumar N, Devasagayam TP. Anticancer property of gallic acid in A549, a human lung adenocarcinoma cell line, and possible mechanisms. J Clin Biochem Nutr. 2011;48(1):85–90. https://doi.org/10.3164/jcbn.11-004FR.

    Article  PubMed  CAS  Google Scholar 

  12. Niemetz R, Gross GG. Enzymology of gallotannin and ellagitannin biosynthesis. Phytochemistry. 2005;66(17):2001–11. https://doi.org/10.1016/j.phytochem.2005.01.009.

    Article  PubMed  CAS  Google Scholar 

  13. Bhattacharya S, Muhammad N, Steele R, Peng G, Ray RB. Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth. Oncotarget. 2016;7(22):33202–9. https://doi.org/10.18632/oncotarget.8898.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002;50(25):7449–54. https://doi.org/10.1021/jf0207530.

    Article  PubMed  CAS  Google Scholar 

  15. Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313–52. https://doi.org/10.3390/molecules15107313.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. De A, De A, Papasian C, Hentges S, Banerjee S, Haque I, Banerjee SK. Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors. PLoS ONE. 2013;8(8):e72748. https://doi.org/10.1371/journal.pone.0072748.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Sourani ZM, Pourgheysari BP, Beshkar PM, Shirzad HP, Shirzad MM. Gallic acid inhibits proliferation and induces apoptosis in lymphoblastic leukemia cell line (C121). Iran J Med Sci. 2016;41(6):525–30.

    Google Scholar 

  18. Yoshino M, Haneda M, Naruse M, Htay HH, Iwata S, Tsubouchi R, Murakami K. Prooxidant action of gallic acid compounds: copper-dependent strand breaks and the formation of 8-hydroxy-2’-deoxyguanosine in DNA. Toxicol In Vitro. 2002;16(6):705–9. https://doi.org/10.1016/s0887-2333(02)00061-9.

    Article  PubMed  CAS  Google Scholar 

  19. Chandramohan Reddy T, Bharat Reddy D, Aparna A, Arunasree KM, Gupta G, Achari C, Reddy GV, Lakshmipathi V, Subramanyam A, Reddanna P. Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation. Toxicol In Vitro. 2012;26(3):396–405. https://doi.org/10.1016/j.tiv.2011.12.018.

    Article  PubMed  CAS  Google Scholar 

  20. Gu R, Zhang M, Meng H, Xu D, Xie Y. Gallic acid targets acute myeloid leukemia via Akt/mTOR-dependent mitochondrial respiration inhibition. Biomed Pharmacother. 2018;105:491–7. https://doi.org/10.1016/j.biopha.2018.05.158.

    Article  PubMed  CAS  Google Scholar 

  21. Aye KT, Wattanapongpitak S, Supawat B, Kothan S, Udomtanakunchai C, Tima S, Pan J, Tungjai M. Gallic acid enhances pirarubicin-induced anticancer in living K562 and K562/Dox leukemia cancer cells through cellular energetic state impairment and P-glycoprotein inhibition. Oncol Rep. 2021;46(4):227. https://doi.org/10.3892/or.2021.8178.

    Article  PubMed  CAS  Google Scholar 

  22. Yang G, Li W, Jiang H, Liang X, Zhao Y, Yu D, Zhou L, Wang G, Tian H, Han F, Cai L, Cui J. Low-dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics. Int J Cancer. 2016;139(10):2157–68. https://doi.org/10.1002/ijc.30235.

    Article  PubMed  CAS  Google Scholar 

  23. Velegzhaninov IO, Shadrin DM, Pylina YI, Ermakova AV, Shostal OA, Belykh ES, Kaneva AV, Ermakova OV, Klokov DY. Differential molecular stress responses to low compared to high doses of ionizing radiation in normal human fibroblasts. Dose Response. 2015. https://doi.org/10.2203/dose-response.14-058.Velegzhaninov.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dauer LT, Brooks AL, Hoel DG, Morgan WF, Stram D, Tran P. Review and evaluation of updated research on the health effects associated with low-dose ionising radiation. Radiat Prot Dosim. 2010;140(2):103–36. https://doi.org/10.1093/rpd/ncq141.

    Article  CAS  Google Scholar 

  25. Luckey TD. Physiological benefits from low levels of ionizing radiation. Health Phys. 1982;43(6):771–89. https://doi.org/10.1097/00004032-198212000-00001.

    Article  PubMed  CAS  Google Scholar 

  26. Feinendegen LE. Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiol. 2005;78(925):3–7. https://doi.org/10.1259/bjr/63353075.

    Article  PubMed  CAS  Google Scholar 

  27. Olivieri G, Bodycote J, Wolff S. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science. 1984;223(4636):594–7. https://doi.org/10.1126/science.6695170.

    Article  PubMed  CAS  Google Scholar 

  28. Jiang H, Xu Y, Li W, Ma K, Cai L, Wang G. Low-dose radiation does not induce proliferation in tumor cells in vitro and in vivo. Radiat Res. 2008;170(4):477–87. https://doi.org/10.1667/rr1132.1.

    Article  PubMed  CAS  Google Scholar 

  29. Li SJ, Liang XY, Li HJ, Yang GZ, Li W, Li Z, Zhou L, Wen X, Yu DH, Cui JW. Low-dose irradiation inhibits proliferation of the p53null type human prostate cancer cells through the ATM/p21 pathway. Int J Mol Med. 2018;41(1):548–54. https://doi.org/10.3892/ijmm.2017.3237.

    Article  PubMed  CAS  Google Scholar 

  30. Chen Z, Sakai K. Enhancement of radiation-induced apoptosis by preirradiation with low-dose X-rays in human leukemia MOLT-4 cells. J Radiat Res. 2004;45(2):239–43. https://doi.org/10.1269/jrr.45.239.

    Article  PubMed  CAS  Google Scholar 

  31. Supawat B, Homnuan P, Kanthawong N, Semrasa N, Tima S, Kothan S, Udomtanakunchai C, Tungjai M. Different responses of normal cells (red blood cells) and cancer cells (K562 and K562/Dox cells) to low-dose 137Cs gamma-rays. Mol Clin Oncol. 2021;14(4):74. https://doi.org/10.3892/mco.2021.2236.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (Δψm) in apoptosis; an update. Apoptosis. 2003;8(2):115–28. https://doi.org/10.1023/A:1022945107762.

    Article  PubMed  CAS  Google Scholar 

  33. Giampazolias E, Tait SW. Mitochondria and the hallmarks of cancer. FEBS J. 2016;283(5):803–14. https://doi.org/10.1111/febs.13603.

    Article  PubMed  CAS  Google Scholar 

  34. Supawat B, Udomtanakunchai C, Kothan S, Tungjai M. The effects of iodinated radiographic contrast media on multidrug-resistant K562/Dox cells: mitochondria impairment and p-glycoprotein inhibition. Cell Biochem Biophys. 2019;77(2):157–63. https://doi.org/10.1007/s12013-019-00868-3.

    Article  PubMed  CAS  Google Scholar 

  35. Supawat B, Moungthong P, Chanloi C, Jindachai N, Tima S, Kothan S, Udomtanakunchai C, Tungjai M. Effects of gadolinium-based magnetic resonance imaging contrast media on red blood cells and K562 cancer cells. J Trace Elem Med Biol. 2020;62:126640. https://doi.org/10.1016/j.jtemb.2020.126640.

    Article  PubMed  CAS  Google Scholar 

  36. Marshall NJ, Goodwin CJ, Holt SJ. A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. Growth Regul. 1995;5(2):69–84.

    PubMed  CAS  Google Scholar 

  37. Kaneko I, Yamada N, Sakuraba Y, Kamenosono M, Tutumi S. Suppression of mitochondrial succinate dehydrogenase, a primary target of beta-amyloid, and its derivative racemized at Ser residue. J Neurochem. 1995;65(6):2585–93. https://doi.org/10.1046/j.1471-4159.1995.65062585.x.

    Article  PubMed  CAS  Google Scholar 

  38. Pereira C, Santos MS, Oliveira C. Metabolic inhibition increases glutamate susceptibility on a PC12 cell line. J Neurosci Res. 1998;51(3):360–70. https://doi.org/10.1002/(sici)1097-4547(19980201)51:3%3c360::Aid-jnr9%3e3.0.Co;2-e.

    Article  PubMed  CAS  Google Scholar 

  39. Surin AM, Sharipov RR, Krasil’nikova IA, Boyarkin DP, Lisina OY, Gorbacheva LR, Avetisyan AV, Pinelis VG. Disruption of functional activity of mitochondria during MTT assay of viability of cultured neurons. Biochem Mosc. 2017;82(6):737–49. https://doi.org/10.1134/S0006297917060104.

    Article  CAS  Google Scholar 

  40. Tungjai M, Phathakanon N, Rithidech KN. Effects of medical diagnostic low-dose X rays on human lymphocytes: mitochondrial membrane potential. Apoptosis Cell Cycle Health Phys. 2017;112(5):458–64. https://doi.org/10.1097/hp.0000000000000647.

    Article  PubMed  CAS  Google Scholar 

  41. Reungpatthanaphong P, Mankhetkorn S. Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol Pharm Bull. 2002;25(12):1555–61. https://doi.org/10.1248/bpb.25.1555.

    Article  PubMed  CAS  Google Scholar 

  42. Kothan S, Dechsupa S, Leger G, Moretti JL, Vergote J, Mankhetkorn S. Spontaneous mitochondrial membrane potential change during apoptotic induction by quercetin in K562 and K562/adr cells. Can J Physiol Pharmacol. 2004;82(12):1084–90. https://doi.org/10.1139/y04-113.

    Article  PubMed  CAS  Google Scholar 

  43. Yang NC, Ho WM, Chen YH, Hu ML. A convenient one-step extraction of cellular ATP using boiling water for the luciferin-luciferase assay of ATP. Anal Biochem. 2002;306(2):323–7. https://doi.org/10.1006/abio.2002.5698.

    Article  PubMed  CAS  Google Scholar 

  44. Xin Y, Zhang HB, Tang TY, Liu GH, Wang JS, Jiang G, Zhang LZ. Low-dose radiation-induced apoptosis in human leukemia K562 cells through mitochondrial pathways. Mol Med Rep. 2014;10(3):1569–75. https://doi.org/10.3892/mmr.2014.2381.

    Article  PubMed  CAS  Google Scholar 

  45. Kianmehr Z, Khorsandi K, Mohammadi M, Hosseinzadeh R. Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells. Melanoma Res. 2020;30(2):136–46. https://doi.org/10.1097/cmr.0000000000000603.

    Article  PubMed  CAS  Google Scholar 

  46. Khorsandi K, Kianmehr Z, Hosseinmardi Z, Hosseinzadeh R. Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis. Cancer Cell Int. 2020;20:18. https://doi.org/10.1186/s12935-020-1100-y.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

Khin TheNu Aye would like to thank the Ph.D. degree program in biomedical sciences, Faculty of Associated Medical Sciences, Chiang Mai University, under the CMU Presidential Scholarship. This research was partially supported by Chiang Mai University and Faculty of Associated Medical Sciences, Chiang Mai University.

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Authors and Affiliations

  1. Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand

    Khin TheNu Aye, Sakornniya Wattanapongpitak, Benjamaporn Supawat, Suchart Kothan, Chatchanok Udomtanakunchai & Montree Tungjai

  2. Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand

    Khin TheNu Aye, Sakornniya Wattanapongpitak, Benjamaporn Supawat, Suchart Kothan, Chatchanok Udomtanakunchai & Montree Tungjai

  3. Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand

    Singkome Tima

  4. Ph.D. Degree Program in Biomedical Sciences, Faculty of Associated Medical Sciences, Chiang Mai University, Under the CMU Presidential Scholarship, Chiang Mai, Thailand

    Khin TheNu Aye

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Aye, K.T., Wattanapongpitak, S., Supawat, B. et al. Effect of pre-low-dose irradiation on anticancer activities of gallic acid in leukemic K562 and K562/Dox cells: cell viability and cellular energetic state studies. Med Oncol 39, 229 (2022). https://doi.org/10.1007/s12032-022-01835-4

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