Anti-Leukemic Effect of Malachite Green-Mediated Photodynamic Therapy by Inducing ER Stress in HL-60 Cells

Year 2024, Volume: 6 Issue: 1, 8 - 13, 31.01.2024

Metin Çalışkan , Gulsen Bayrak , Sercin Özlem Çalışkan

https://doi.org/10.37990/medr.1368570

Abstract

Aim: Our objective is to explore the relationship between the anti-leukemic impact of malachite green-mediated photodynamic therapy (PDT) and the induction of endoplasmic reticulum (ER) stress in acute promyelocytic leukemia cells (HL-60).
Material and Method: For one hour the cells were incubated with different concentrations (3.125, 1.56, 0.78, 0.39, 0.195, 0.0975, 0.04875 μM) of malachite green and then were exposed to 0.47 mW/cm2 irradiance and 0.84 J/cm2 fluence for 30 minutes. Also, HL-60 cells were exposed to PDT with light only and both in the presence or absence of malachite green. MTT assay was used to determine cell viability, and immunocytochemical staining was used to detect the expression of ER stress markers Protein Kinase R-like ER Kinase (PERK) and Glucose-regulated protein 78 (GRP78).
Results: The cell viability of the treatment group (combination of malachite green and light) was significantly decreased compared to the malachite green, control group, and light control. Moreover, immunocytochemical staining scores showed that PERK and GRP78 were significantly upregulated in the treatment group compared with other groups.
Conclusion: Our results indicate that ER stress may contribute to the cytotoxicity occurring in HL-60 cancer cells after malachite green-mediated PDT. Future studies will be crucial in shedding light on the molecular mechanisms underlying ER stress that may occur after PDT. These findings lay the foundation for further investigations in this area.

Keywords

Acute myeloid leukemia, malachite green, photodynamic therapy, ER stress, Protein Kinase R-like ER Kinase, Glucose-regulated protein 78

Ethical Statement

Çalışmanın metodolojik yapısının "hücre kültürü çalışması" olması nedeniyle Dünya Tabipleri Birliği Helsinki Bildirgesi "İnsanlar Üzerinde Yapılan Tıbbi Araştırmalarla İlgili Etik İlkeleri" gereğince etik kurul onayı gerektirmemektedir.

Supporting Institution

Bu çalışmada herhangi bir finansal destek alınmamıştır.

References

• Stubbins RJ, Stamenkovic M, Roy C, et al. Incidence and socioeconomic factors in older adults with acute myeloid leukaemia: real-world outcomes from a population-based cohort. Eur J Haematol. 2022;108:437-45.
• Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2016;66:271-89.
• Yano S, Hirohara S, Obata M, et al. Current states and future views in photodynamic therapy. J Photochem Photobiol C. 2011;12:46-67.
• Castano AP, Mroz P, Hamblin MR. Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer. 2006;6:535-45.
• Moan J, Berg K. The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochem Photobiol. 1991;53:549-53.
• Wilson BC, Patterson MS. The physics, biophysics and technology of photodynamic therapy. Phys Med Biol. 2008;53:R61-109.
• Araki K, Nagata K. Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol. 2011;3:a007526.
• 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.
• Li KT, Chen Q, Wang DW, et al. Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of AE-PDT in MG63 cells. Cancer Med. 2016;5:3186-93.
• 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.
• Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61:250-81.
• 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.
• Riezzo I, Pascale N, Russa RL, et al. Donor selection for allogenic hemopoietic stem cell transplantation clinical and ethical considerations. Stem Cells Int. 2017;2017:5250790.
• Huang H, Chen Y, Chen W, et al. Purging efficacy of ZnPcH1-based photodynamic therapy on chronic myeloid leukemia bone marrow. Int J Lab Hematol. 2011;33:477-82.
• Caliskan-Ozlem S, Gurel-Karadag A, Uzunok B, et al. Antileukemic potential of Nile blue-mediated photodynamic therapy on HL60 human myeloid leukemia cells. Turkish Journal of Biology. 2023;47:276-89.
• Pluskalova M, Peslova G, Grebenova D, et al. Photodynamic treatment (ALA-PDT) suppresses the expression of the oncogenic Bcr-Abl kinase and affects the cytoskeleton organization in K562 cells. J Photochem Photobiol B Biol. 2006;83:205-12.
• Xu Y, Wang D, Zhuang Z, et al. Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation. Mol Med Rep. 2015;12:6475-82.
• 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.
• Philchenkov AA, Shishko ED, Zavelevich MP, et al. Photodynamic responsiveness of human leukemia Jurkat/A4 cells with multidrug resistant phenotype. Exp Oncol. 2014;36:241-5.
• Verfaillie T, Rubio N, Garg AD, et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ. 2012;19:1880-91.
• Buytaert E, Callewaert G, Hendrickx N, et al. Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy. FASEB J. 2006;20:756-8.
• Tameire F, Verginadis II, Koumenis C. Cell intrinsic and extrinsic activators of the unfolded protein response in cancer: Mechanisms and targets for therapy. Semin Cancer Biol. 2015;33:3-15.
• Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta. 2013;1833:3460-70.
• Gong J, Wang XZ, Wang T, et al. Molecular signal networks and regulating mechanisms of the unfolded protein response. J. Zhejiang Univ Sci B. 2017;18:1-14.
• Chiarante N, García Vior MC, Rey O, et al. Lysosomal permeabilization and endoplasmic reticulum stress mediate the apoptotic response induced after photoactivation of a lipophilic zinc(II) phthalocyanine. Int J Biochem Cell Biol. 2018;103:89-98.
• Zuo Q, Yunsheng O, Zhong S, et al. Targeting GRP78 enhances the sensitivity of HOS osteosarcoma cells to pyropheophorbide-α methyl ester-mediated photodynamic therapy via the Wnt/β-catenin signaling pathway. Acta Biochim Biophys Sin (Shanghai). 2021;53:1387-97.
• Moserova I, Kralova J. Role of ER Stress Response in Photodynamic Therapy: ROS Generated in Different Subcellular Compartments Trigger Diverse Cell Death Pathways. PLoS One. 2012; 7:e32972.
• Chen J, Huang JH, Wang Z, et al. Endoplasmic reticulum stress-mediated autophagy contributes to 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium-mediated photodynamic therapy via the PERK-eIF2alpha pathway. Onco Targets Ther. 2018;11:4315-25.
• Zhu J, Tian S, Li KT, et al. Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress-induced autophagy in vitro and vivo. Cancer Med. 2018;7:1908-20.