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Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation

  • Authors:
    • Yixiao Xu
    • Dexuan Wang
    • Zhizhi Zhuang
    • Keke Jin
    • Lvzhen Zheng
    • Qing Yang
    • Kunyuan Guo
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Pediatrics, The Second Affiliated and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6475-6482
    |
    Published online on: August 27, 2015
       https://doi.org/10.3892/mmr.2015.4258
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Abstract

Hypericin (Hyp) is traditionally used as an antidepressant and antiviral agent. It selectively accumulates in spheroids and is also used as a photosensitizer in the photodynamic therapy of cancer. The present study aimed to investigate the cytotoxic effect of Hyp‑mediated photodynamic therapy (Hyp‑PDT) on cell growth and apoptosis of K562 leukemia cells, and to examine the underlying mechanisms. Hyp‑PDT was performed with different light intensities (0.1, 0.3 and 0.5 mW/cm2), different concentrations of Hyp (0, 0.2, 0.4 and 0.8 µg/ml) and different durations of irradiation (0, 2, 4 and 8 min) in order to select the optimal conditions for subsequent experiments. A concentration of 0.4 µg/ml Hyp with a 5 h drug‑light interval and 4 min irradiation at 0.3 mW/cm2 light intensity was selected as the optimal conditions. The effects of Hyp‑PDT on apoptosis were determined by detecting morphological changes under microscopy and by performing western blot analysis. The results revealed that Hyp‑PDT suppressed cell viability in a light intensity‑, dose‑ and irradiation duration‑dependent manner. The expression levels of cleaved caspase‑9, cleaved caspase‑3 and phosphorylated‑C‑Jun N terminal kinase (JNK)l were significantly upregulated following Hyp‑PDT. These results indicated that Hyp‑PDT decreased cell viability and induced mitochondria‑caspase‑dependent apoptosis in the K562 cells through regulation of the JNK pathway. These findings suggest that Hyp-PDT may be developed as an effective treatment for leukemia.
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1 

Panzarini E, Inguscio V, Fimia GM and Dini L: Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of damage-associated molecular patterns (DAMPs) in human HeLa cells. PLoS One. 9:e1057782014. View Article : Google Scholar : PubMed/NCBI

2 

Martirosyan AS, Vardapetyan HR, Tiratsuyan SG and Hovhannisyan AA: Biphasic dose-response of antioxidants in hypericin-induced photohemolysis. Photodiagnosis Photodyn Ther. 8:282–287. 2011.PubMed/NCBI

3 

Plaetzer K, Krammer B, Berlanda J, Berr F and Kiesslich T: Photophysics and photochemistry of photodynamic therapy: Fundamental aspects. Lasers Med Sci. 24:259–268. 2009. View Article : Google Scholar

4 

Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, et al: Photodynamic therapy of cancer: An update. CA Cancer J Clin. 61:250–281. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Lee JY, Diaz RR, Cho KS, Lim MS, Chung JS, Kim WT, Ham WS and Choi YD: Efficacy and safety of photodynamic therapy for recurrent, high grade nonmuscle invasive bladder cancerrefractory or intolerant to bacille Calmette-Guérin immunotherapy. J Urol. 190:1192–1199. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Gray J and Fullarton GM: Long term efficacy of photodynamic therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus. Photodiagnosis Photodyn Ther. 10:561–565. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Lo VC, Akens MK, Wise-Milestone L, Yee AJ, Wilson BC and Whyne CM: The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy. J Orthop Res. 31:1398–1405. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Krammer B and Verwanger T: Molecular response to hypericin-induced photodamage. Curr Med Chem. 19:793–798. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Nakajima N and Kawashima N: A basic study on hypericin-PDT in vitro. Photodiagnosis Photodyn Ther. 9:196–203. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Lima AM, Pizzol CD, Monteiro FB, Creczynski-Pasa TB, Andrade GP, Ribeiro AO and Perussi JR: Hypericin encapsulated in solid lipid nanoparticles: Phototoxicity and photodynamic efficiency. J Photochem Photobiol B. 125:146–154. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Ehrenberg B, Anderson JL and Foote CS: Kinetics and yield of singlet oxygen photosensitized by hypericin in organic and biological media. Photochem Photobiol. 68:135–140. 1998. View Article : Google Scholar : PubMed/NCBI

12 

Kleemann B, Loos B, Scriba TJ, Lang D and Davids LM: St John's Wort (Hypericum perforatum L.) photomedicine: Hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS One. 9:e1037622014. View Article : Google Scholar : PubMed/NCBI

13 

Zheng Y, Le V, Cheng Z, Xie S, Li H, Tian J and Liu J: Development of rapid and highly sensitive HSPA1A promoter-driven luciferase reporter system for assessing oxidative stress associated with low-dose photodynamic therapy. Cell Stress Chaperones. 18:203–213. 2013. View Article : Google Scholar :

14 

Tan B, Anaka M, Deb S, Freyer C, Ebert LM, Chueh AC, Al-Obaidi S, Behren A, Jayachandran A, Cebon J, Chen W and Mariadason JM: FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis. Oncotarget. 15:264–276. 2014. View Article : Google Scholar

15 

Miccoli L, Beurdeley-Thomas A, De Pinieux G, Sureau F, Oudard S, Dutrillaux B and Poupon MF: Light-induced photo-activation of hypericin affects the energy metabolism of human glioma cells by inhibiting hexokinase bound to mitochondria. Cancer Res. 58:5777–5786. 1998.PubMed/NCBI

16 

Chen B, Roskams T, Xu Y, Agostinis P and de Witte PA: Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model. Int J Cancer. 98:284–290. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Roelants M, Van Cleynenbreugel B, Lerut E, Van Poppel H and de Witte PA: Human serum albumin as key mediator of the differential accumulation of hypericin in normal urothelial cell spheroids versus urothelial cell carcinoma spheroids. Photochem Photobiol Sci. 10:151–159. 2011. View Article : Google Scholar

18 

Kim HB, Kim MJ, Lee SH, Lee JW, Bae JH, Kim DW, Dao TT, Oh WK, Kang CD and Kim SH: Amurensin G, a novel SIRT1 inhibitor, sensitizes TRAIL-resistant human leukemic K562 cells to TRAIL-induced apoptosis. Biochem Pharmacol. 84:402–410. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Fox FE, Niu Z, Tobia A and Rook AH: Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed and malignant T lymphocytes: Implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders. J Invest Dermatol. 111:327–332. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Rook AH, Wood GS, Duvic M, Vonderheid EC, Tobia A and Cabana B: A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis. J Am Acad Dermatol. 63:984–990. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Berlanda J, Kiesslich T, Oberdanner CB, Obermair FJ, Krammer B and Plaetzer K: Characterization of apoptosis induced by photodynamic treatment with hypericin in A431 human epidermoid carcinoma cells. J Environ Pathol Toxicol Oncol. 25:173–188. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Buytaert E, Callewaert G, Hendrickx N, Scorrano L, Hartmann D, Missiaen L, Vandenheede JR, Heirman I, Grooten J and Agostinis P: Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy. FASEB J. 20:756–758. 2006.PubMed/NCBI

23 

Sanovic R, Krammer B, Grumboeck S and Verwanger T: Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photo-dynamic treatment with hypericin. Int J Oncol. 35:921–939. 2009.PubMed/NCBI

24 

Ali SM, Chee SK, Yuen GY and Olivo M: Hypocrellins and Hypericin induced apoptosis in human tumor cells: A possible role of hydrogen peroxide. Int J Mol Med. 9:461–472. 2002.PubMed/NCBI

25 

Koval J, Mikes J, Jendzelovský R, Kello M, Solár P and Fedorocko P: Degradation of HER2 receptor through hypericin-mediated photodynamic therapy. Photochem Photobiol. 86:200–205. 2010. View Article : Google Scholar

26 

Skulachev VP: The programmed death phenomena, aging and the Samurai law of biology. Exp Gerontol. 36:995–1024. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Dhanasekaran DN and Reddy EP: JNK signaling in apoptosis. Oncogene. 27:6245–6251. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Varfolomeev EE and Ashkenazi A: Tumor necrosis factor: An apoptosis JuNKie? Cell. 116:491–497. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Feng Q, Cao HL, Xu W, Li XR, Ren YQ and Du LF: Apoptosis induced by genipin in human leukemia K562 cells: Involvement of c-Jun N-terminal kinase in G2/M arrest. Acta Pharmacol Sin. 32:519–527. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Chen YJ, Liu WH, Kao PH, Wang JJ and Chang LS: Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells. Toxicon. 55:1306–1316. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Takamura M, Matsuda Y, Yamagiwa S, Tamura Y, Honda Y, Suzuki K, Ichida T and Aoyagi Y: An inhibitor of c-Jun NH2-terminal kinase, SP600125, protects mice from D-galactosamine/lipopolysaccharide-induced hepatic failure by modulating BH3-only proteins. Life Sci. 80:1335–1344. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Lee S, Park HS, Notsu Y, Ban HS, Kim YP, Ishihara K, Hirasawa N, Jung SH, Lee YS, Lim SS, et al: Effects of hyperin, isoquercitrin and quercetin on lipopolysaccharide-induced nitrite production in rat peritoneal macrophages. Phytother Res. 22:1552–1556. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Zhang Z, Sethiel MS, Shen W, Liao S and Zou Y: Hyperoside downregulates the receptor for advanced glycation end products (RAGE) and promotes proliferation in ECV304 cells via the c-Jun N-terminal kinases (JNK) pathway following stimulation by advanced glycation end-products in vitro. Int J Mol Sci. 14:22697–22707. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Wang D, Zhuang Z, Jin K, Zheng L, Yang Q and Guo K: Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation. Mol Med Rep 12: 6475-6482, 2015.
APA
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., & Guo, K. (2015). Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation. Molecular Medicine Reports, 12, 6475-6482. https://doi.org/10.3892/mmr.2015.4258
MLA
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., Guo, K."Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation". Molecular Medicine Reports 12.5 (2015): 6475-6482.
Chicago
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., Guo, K."Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation". Molecular Medicine Reports 12, no. 5 (2015): 6475-6482. https://doi.org/10.3892/mmr.2015.4258
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Wang D, Zhuang Z, Jin K, Zheng L, Yang Q and Guo K: Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation. Mol Med Rep 12: 6475-6482, 2015.
APA
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., & Guo, K. (2015). Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation. Molecular Medicine Reports, 12, 6475-6482. https://doi.org/10.3892/mmr.2015.4258
MLA
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., Guo, K."Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation". Molecular Medicine Reports 12.5 (2015): 6475-6482.
Chicago
Xu, Y., Wang, D., Zhuang, Z., Jin, K., Zheng, L., Yang, Q., Guo, K."Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation". Molecular Medicine Reports 12, no. 5 (2015): 6475-6482. https://doi.org/10.3892/mmr.2015.4258
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