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Investigation of Endoplasmic Reticulum Stress and Apoptosis Caused by Malachite Green-Mediated Sonodynamic Therapy in HL60 Cells

Year 2024, Volume: 6 Issue: 1, 89 - 94, 31.01.2024
https://doi.org/10.37990/medr.1395057

Abstract

Aim: Sonodynamic antitumor therapy is a promising, novel method for the treatment of cancer. To determine the effects of malachite green (MG) in the presence of ultrasound (US), MG was tested in vitro on HL60 cells at different concentrations as a sonodynamic compound. We investigated cell viability, morphology, and the occurrence of ER stress after MG-mediated sonodynamic therapy (SDT) in HL60 cells.
Aim: Sonodynamic antitumor therapy is a promising, novel method for the treatment of cancer. To determine the effects of malachite green (MG) in the presence of ultrasound (US), MG was tested in vitro on HL60 cells at different concentrations as a sonodynamic compound. We investigated cell viability, morphology, and the occurrence of endoplasmic reticulum (ER) stress after MG-mediated sonodynamic therapy (SDT) in HL60 cells.
Material and Method: Four groups were formed, including a control group, a group subjected to ultrasound (US) only, a group treated with various concentrations of MG, and a group treated with US using the same concentrations. The cells were treated with 1MHz ultrasound at 2 W/cm2 for 3 minutes. The assessment of cell viability was conducted 24 hours post-treatment through the utilization of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell morphology and apoptotic index were determined using Giemsa staining, while GRP78 and PERK expressions were determined through immunocytochemistry staining.
Results: The cell cytotoxicity of HL60 cells significantly increased after MG-mediated sonodynamic therapy. After treatment, apoptotic cells with micronuclei were observed morphologically. Significant levels of GRP78 and PERK expression were observed in all groups, except for PERK expression in the US group, compared to the control group.
Conclusion: The induction of ER stress, accompanied by intense apoptosis and a marked decrease in cell viability, demonstrates the potential of MG-mediated sonodynamic therapy in cancer treatment. Investigating ER stress as a molecular target may contribute to improving the treatment method.

Ethical Statement

Since the methodological structure of the study is a "cell culture study", it does not require ethics committee approval in accordance with the World Medical Association Declaration of Helsinki "Ethical Principles for Medical Research on Humans"

Supporting Institution

The authors declared that this study has received no financial support.

References

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  • Zou L, Wang H, He B, et al. Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics.Theranostics. 2016;6:762-72.
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  • Qian X, Zheng Y, Chen Y. Micro/nanoparticle-augmented sonodynamic therapy (SDT): breaking the depth shallow of photoactivation. Adv Mater. 2016;28:8097-129.
  • Yumita N, Nishigaki R, Umemura K, Umemura S. Hematoporphyrin as a sensitizer of cell-damaging effect of ultrasound. Jpn J Cancer Res.1989;80:219-22.
  • Gong F, Cheng L, Yang N, et al. Ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles for depletion of endogenous GSH and enhanced sonodynamic cancer therapy. Adv Mater. 2019;31:1900730.
  • Son S, Kim JH, Wang X, et al. Multifunctional sonosensitizers in sonodynamic cancer therapy. Chem Soc Rev. 2020;49:3244-61.
  • Chen H, Zhou X, Gao Y, et al. Recent progress in development of new sonosensitizers for sonodynamic cancer therapy. Drug DiscovToday. 2014;19:502-9.
  • Yu J, Guo Z, Yan J, et al. Gastric acid-responsive ROS nanogenerators for effective treatment of helicobacter pylori infection without disrupting homeostasis of intestinal flora. Adv Sci.2023;10:e2206957.
  • Liang S, Deng X, Ma PA, et al. Recent advances in nanomaterial-assisted combinational sonodynamic cancer therapy. Adv Mater. 2020;32:e2003214.
  • Canavese G, Ancona A, Racca L, et al. Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer. Chem Eng J. 2018;340:155-72.
  • Araki K, Nagata K. Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol. 2011;3:a007526. Erratum in: Cold Spring Harb Perspect Biol. 2012;4:a015438.
  • Li D, Li L, Li P, et al. Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress. Onco Targets Ther. 2015;8:703-11.
  • Lin S, Yang L, Shi H, et al. Endoplasmic reticulum-targeting photosensitizer Hypericin confers chemo-sensitization towards oxaliplatin through inducing pro-death autophagy. Int J Biochem Cell Biol. 2017;87:54-68.
  • Firczuk M, Gabrysiak M, Barankiewicz J, et al. GRP78-targeting subtilase cytotoxin sensitizes cancer cells to photodynamic therapy. Cell Death Dis. 2013;4:e741.
  • Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519-29.
  • Sun XF, Wang SG, Liu XW, et al. Biosorption of malachite green from aqueous solutions onto aerobic granules: kinetic on equilibrium studies. Bioresour Technol. 2008;99:3475-83.
  • Montes de Oca MN, Vara J, Milla L, et al. Physicochemical properties and photodynamic activity of novel derivatives of triarylmethane and thiazine. Arch Pharm (Weinheim). 2013;346:255-65.
  • Caliskan-Ozlem S, Duran ÖF, Aslan C, et al. Therapeutic efficacy of malachite green-based photodynamic therapy in acute myeloid leukemia. J Contemp Med. 2023;13:305-11.
  • Yumita N, Iwase Y, Nishi K, et al. Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative. Theranostic. 2012;2:880-8.
  • Cizkova K, Foltynkova T, Gachechiladze M, et al. Comparative analysis of immunohistochemical staining intensity determined by light microscopy, Image J and QuPath in placental hofbauer cells. Acta Histochem Cytochem. 2021;54:21-9.
  • Li Y, Su X, Wang X, et al. Cytotoxic effect of protoporphyrin IX to human leukemia U937 cells under ultrasonic irradiation. Cell Physiol Biochem. 2014;33:1186-96.
  • Li Y, Wang P, Wang X, et al. Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells. Ultrasound Med Biol. 2014;40:990-1000.
  • Yumita N, Okudaira K, Momose Y, Umemura S. Sonodynamically induced apoptosis and active oxygen generation by gallium-porphyrin complex, ATX-70. Cancer Chemother Pharmacol. 2010;66:1071-8.
  • Yumita N, Watanabe T, Chen FS, et al. Induction of apoptosis by functionalized fullerene-based sonodynamic therapy in HL-60 cells. Anticancer Res. 2016;36:2665-74.
  • Su X, Wang X, Zhang K, et al. Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX. Gen Physiol Biophys. 2016;35:155-64.
  • Su X, Wang P, Wang X, et al. Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy. Int J Radiat Biol. 2013;89:915-27.
  • Trendowski M, Yu G, Wong V, et al. The real deal: using cytochalasin B in sonodynamic therapy to preferentially damage leukemia cells. Anticancer Res. 2014;34:2195-202.
Year 2024, Volume: 6 Issue: 1, 89 - 94, 31.01.2024
https://doi.org/10.37990/medr.1395057

Abstract

References

  • Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics. Cancer J Clin. 2022;72:409-36.
  • Zou L, Wang H, He B, et al. Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics.Theranostics. 2016;6:762-72.
  • Correia JH, Rodrigues JA, Pimenta S, et al Photodynamic therapy review: principles, photosensitizers, applications, and future directions. Pharmaceutics. 2021;13:1332.
  • Qian X, Zheng Y, Chen Y. Micro/nanoparticle-augmented sonodynamic therapy (SDT): breaking the depth shallow of photoactivation. Adv Mater. 2016;28:8097-129.
  • Yumita N, Nishigaki R, Umemura K, Umemura S. Hematoporphyrin as a sensitizer of cell-damaging effect of ultrasound. Jpn J Cancer Res.1989;80:219-22.
  • Gong F, Cheng L, Yang N, et al. Ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles for depletion of endogenous GSH and enhanced sonodynamic cancer therapy. Adv Mater. 2019;31:1900730.
  • Son S, Kim JH, Wang X, et al. Multifunctional sonosensitizers in sonodynamic cancer therapy. Chem Soc Rev. 2020;49:3244-61.
  • Chen H, Zhou X, Gao Y, et al. Recent progress in development of new sonosensitizers for sonodynamic cancer therapy. Drug DiscovToday. 2014;19:502-9.
  • Yu J, Guo Z, Yan J, et al. Gastric acid-responsive ROS nanogenerators for effective treatment of helicobacter pylori infection without disrupting homeostasis of intestinal flora. Adv Sci.2023;10:e2206957.
  • Liang S, Deng X, Ma PA, et al. Recent advances in nanomaterial-assisted combinational sonodynamic cancer therapy. Adv Mater. 2020;32:e2003214.
  • Canavese G, Ancona A, Racca L, et al. Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer. Chem Eng J. 2018;340:155-72.
  • Araki K, Nagata K. Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol. 2011;3:a007526. Erratum in: Cold Spring Harb Perspect Biol. 2012;4:a015438.
  • Li D, Li L, Li P, et al. Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress. Onco Targets Ther. 2015;8:703-11.
  • Lin S, Yang L, Shi H, et al. Endoplasmic reticulum-targeting photosensitizer Hypericin confers chemo-sensitization towards oxaliplatin through inducing pro-death autophagy. Int J Biochem Cell Biol. 2017;87:54-68.
  • Firczuk M, Gabrysiak M, Barankiewicz J, et al. GRP78-targeting subtilase cytotoxin sensitizes cancer cells to photodynamic therapy. Cell Death Dis. 2013;4:e741.
  • Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519-29.
  • Sun XF, Wang SG, Liu XW, et al. Biosorption of malachite green from aqueous solutions onto aerobic granules: kinetic on equilibrium studies. Bioresour Technol. 2008;99:3475-83.
  • Montes de Oca MN, Vara J, Milla L, et al. Physicochemical properties and photodynamic activity of novel derivatives of triarylmethane and thiazine. Arch Pharm (Weinheim). 2013;346:255-65.
  • Caliskan-Ozlem S, Duran ÖF, Aslan C, et al. Therapeutic efficacy of malachite green-based photodynamic therapy in acute myeloid leukemia. J Contemp Med. 2023;13:305-11.
  • Yumita N, Iwase Y, Nishi K, et al. Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative. Theranostic. 2012;2:880-8.
  • Cizkova K, Foltynkova T, Gachechiladze M, et al. Comparative analysis of immunohistochemical staining intensity determined by light microscopy, Image J and QuPath in placental hofbauer cells. Acta Histochem Cytochem. 2021;54:21-9.
  • Li Y, Su X, Wang X, et al. Cytotoxic effect of protoporphyrin IX to human leukemia U937 cells under ultrasonic irradiation. Cell Physiol Biochem. 2014;33:1186-96.
  • Li Y, Wang P, Wang X, et al. Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells. Ultrasound Med Biol. 2014;40:990-1000.
  • Yumita N, Okudaira K, Momose Y, Umemura S. Sonodynamically induced apoptosis and active oxygen generation by gallium-porphyrin complex, ATX-70. Cancer Chemother Pharmacol. 2010;66:1071-8.
  • Yumita N, Watanabe T, Chen FS, et al. Induction of apoptosis by functionalized fullerene-based sonodynamic therapy in HL-60 cells. Anticancer Res. 2016;36:2665-74.
  • Su X, Wang X, Zhang K, et al. Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX. Gen Physiol Biophys. 2016;35:155-64.
  • Su X, Wang P, Wang X, et al. Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy. Int J Radiat Biol. 2013;89:915-27.
  • Trendowski M, Yu G, Wong V, et al. The real deal: using cytochalasin B in sonodynamic therapy to preferentially damage leukemia cells. Anticancer Res. 2014;34:2195-202.
There are 28 citations in total.

Details

Primary Language English
Subjects Medical Physics, Medical and Biological Physics (Other)
Journal Section Original Articles
Authors

Metin Çalışkan 0000-0002-9243-4943

Gulsen Bayrak 0000-0002-1397-7203

Serçin Özlem Çalışkan 0000-0001-8464-5487

Publication Date January 31, 2024
Submission Date November 27, 2023
Acceptance Date December 23, 2023
Published in Issue Year 2024 Volume: 6 Issue: 1

Cite

AMA Çalışkan M, Bayrak G, Özlem Çalışkan S. Investigation of Endoplasmic Reticulum Stress and Apoptosis Caused by Malachite Green-Mediated Sonodynamic Therapy in HL60 Cells. Med Records. January 2024;6(1):89-94. doi:10.37990/medr.1395057

17741

Chief Editors

Assoc. Prof. Zülal Öner
Address: İzmir Bakırçay University, Department of Anatomy, İzmir, Türkiye

Assoc. Prof. Deniz Şenol
Address: Düzce University, Department of Anatomy, Düzce, Türkiye

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