Photosensitizing Effects of Hypericin on Head Neck Squamous Cell Carcinoma in Vitro

Overview

Journal Eur Arch Otorhinolaryngol

Specialty Otorhinolaryngology

Date 2014 Apr 2

PMID 24687800

Citations 3

Authors

Wiebke Laffers

Ann-Christin Busse

Jens Mahrt

Phuc Nguyen

Andreas O H Gerstner

Friedrich Bootz

Johannes T Wessels

Affiliations

Soon will be listed here.

Abstract

Clinical outcome of patients suffering from head neck squamous cell carcinomas is still poor due to recurrent disease and surgical limitations. There is still a demand for multimodality approaches and new therapeutic options. Hypericin is a promising phototoxic drug which was investigated for its effects on head neck squamous cell carcinoma cells in vitro. FaDu cells incubated with or without hypericin were illuminated (450-700 nm, 50,000 lx) for different time periods. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide- and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to score metabolic and apoptotic activity. Even after the shortest illumination FaDu cells incubated with hypericin showed massive reduction of metabolism and excessive apoptosis. This was present even with the lowest hypericin concentration. Cells without hypericin or without illumination were not affected. These photosensitizing effects of hypericin could be suitable for clinical application and could lead to the development of an intraoperative photodynamic therapy of head neck squamous cell carcinomas.

Citing Articles

Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review.

Fiegler-Rudol J, Zieba N, Turski R, Misiolek M, Wiench R Biomedicines. 2025; 13(1).

PMID: 39857765 PMC: 11759840. DOI: 10.3390/biomedicines13010181.

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers-New Aspects and Revelations.

Hubinger L, Wetzig K, Runge R, Hartmann H, Tillner F, Tietze K Pharmaceutics. 2024; 16(4).

PMID: 38675195 PMC: 11054706. DOI: 10.3390/pharmaceutics16040534.

Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel -Glucosidase Inhibitor.

Dong Q, Hu N, Yue H, Wang H Molecules. 2021; 26(15).

PMID: 34361714 PMC: 8348433. DOI: 10.3390/molecules26154566.

Susceptibility of Melanoma Skin Cancer to Photoactivated Hypericin versus Aluminium(III) Phthalocyanine Chloride Tetrasulphonate.

Ndhundhuma I, Abrahamse H Biomed Res Int. 2017; 2017:5407012.

PMID: 29147654 PMC: 5632892. DOI: 10.1155/2017/5407012.

References

Kascakova S, Nadova Z, Mateasik A, Mikes J, Huntosova V, Refregiers M . High level of low-density lipoprotein receptors enhance hypericin uptake by U-87 MG cells in the presence of LDL. Photochem Photobiol. 2008; 84(1):120-7. DOI: 10.1111/j.1751-1097.2007.00207.x. View

Gyenge E, Forny P, Luscher D, Laass A, Walt H, Maake C . Effects of hypericin and a chlorin based photosensitizer alone or in combination in squamous cell carcinoma cells in the dark. Photodiagnosis Photodyn Ther. 2012; 9(4):321-31. DOI: 10.1016/j.pdpdt.2012.03.006. View

Karioti A, Bilia A . Hypericins as potential leads for new therapeutics. Int J Mol Sci. 2010; 11(2):562-94. PMC: 2852855. DOI: 10.3390/ijms11020562. View

Siboni G, Weitman H, Freeman D, Mazur Y, Malik Z, Ehrenberg B . The correlation between hydrophilicity of hypericins and helianthrone: internalization mechanisms, subcellular distribution and photodynamic action in colon carcinoma cells. Photochem Photobiol Sci. 2003; 1(7):483-91. DOI: 10.1039/b202884k. View

Ritz R, Muller M, Weller M, Dietz K, Kuci S, Roser F . Hypericin: a promising fluorescence marker for differentiating between glioblastoma and neurons in vitro. Int J Oncol. 2005; 27(6):1543-9. View

Theodossiou T, Hothersall J, de Witte P, Pantos A, Agostinis P . The multifaceted photocytotoxic profile of hypericin. Mol Pharm. 2009; 6(6):1775-89. DOI: 10.1021/mp900166q. View

Huygens A, Kamuhabwa A, Roskams T, Van Cleynenbreugel B, van Poppel H, de Witte P . Permeation of hypericin in spheroids composed of different grade transitional cell carcinoma cell lines and normal human urothelial cells. J Urol. 2005; 174(1):69-72. DOI: 10.1097/01.ju.0000162037.49102.56. View

Kim A, Suh J, Sercarz J, Abemayor E, Head C, Funk G . Salvage surgery with free flap reconstruction: factors affecting outcome after treatment of recurrent head and neck squamous carcinoma. Laryngoscope. 2007; 117(6):1019-23. DOI: 10.1097/MLG.0b013e3180536705. View

Thong P, Olivo M, Chin W, Bhuvaneswari R, Mancer K, Soo K . Clinical application of fluorescence endoscopic imaging using hypericin for the diagnosis of human oral cavity lesions. Br J Cancer. 2009; 101(9):1580-4. PMC: 2778520. DOI: 10.1038/sj.bjc.6605357. View

10.

Traynor N, Beattie P, Ibbotson S, Moseley H, Ferguson J, Woods J . Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. John's Wort supplements and high dose UVA-1 therapy. Toxicol Lett. 2005; 158(3):220-4. DOI: 10.1016/j.toxlet.2005.03.012. View

11.

RANGAN S . A new human cell line (FaDu) from a hypopharyngeal carcinoma. Cancer. 1972; 29(1):117-21. DOI: 10.1002/1097-0142(197201)29:1<117::aid-cncr2820290119>3.0.co;2-r. View

12.

Blank M, Lavie G, Mandel M, Hazan S, Orenstein A, Meruelo D . Antimetastatic activity of the photodynamic agent hypericin in the dark. Int J Cancer. 2004; 111(4):596-603. DOI: 10.1002/ijc.20285. View

13.

Seitz G, Krause R, Fuchs J, Heitmann H, Armeanu S, Ruck P . In vitro photodynamic therapy in pediatric epithelial liver tumors promoted by hypericin. Oncol Rep. 2008; 20(5):1277-82. View

14.

Ali S, Olivo M . Mechanisms of action of phenanthroperylenequinones in photodynamic therapy (review). Int J Oncol. 2003; 22(6):1181-91. View

15.

Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M . Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol. 2010; 2:9. PMC: 2882907. DOI: 10.1186/1758-3284-2-9. View

16.

Buytaert E, Dewaele M, Agostinis P . Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim Biophys Acta. 2007; 1776(1):86-107. DOI: 10.1016/j.bbcan.2007.07.001. View

17.

Agostinis P, Vantieghem A, Merlevede W, de Witte P . Hypericin in cancer treatment: more light on the way. Int J Biochem Cell Biol. 2002; 34(3):221-41. DOI: 10.1016/s1357-2725(01)00126-1. View

18.

Wessels J, Busse A, Rave-Frank M, Zanker S, Hermann R, Grabbe E . Photosensitizing and radiosensitizing effects of hypericin on human renal carcinoma cells in vitro. Photochem Photobiol. 2008; 84(1):228-35. DOI: 10.1111/j.1751-1097.2007.00225.x. View

19.

Sanovic R, Krammer B, Grumboeck S, Verwanger T . Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin. Int J Oncol. 2009; 35(4):921-39. DOI: 10.3892/ijo_00000407. View

20.

Ritz R, Daniels R, Noell S, Feigl G, Schmidt V, Bornemann A . Hypericin for visualization of high grade gliomas: first clinical experience. Eur J Surg Oncol. 2012; 38(4):352-60. DOI: 10.1016/j.ejso.2011.12.021. View