Molecular response to hypericin-induced photodamage

Current Medicinal Chemistry

Volumn 19, Issue 6, 2012, Pages 793-798

  Krammer, B ^a   Verwanger, T ^a  

^a UNIVERSITY OF SALZBURG   (Austria)

Author keywords

Apoptosis; Autophagy; Hypericin; Molecular; Photodynamic therapy; Reactive oxygen species; Signalling pathway

Indexed keywords

ANTINEOPLASTIC AGENT; HYPERICIN;

APOPTOSIS; AUTOPHAGY; CELL DEATH; CELL MEMBRANE; DEPRESSION; ENDOPLASMIC RETICULUM STRESS; FLUORESCENCE ANALYSIS; GROWTH STIMULATION; HUMAN; IRRADIATION; MOLECULAR DYNAMICS; NONHUMAN; PHOTODAMAGE; PHOTODYNAMIC THERAPY; PHOTOSENSITIVITY; PHOTOTOXICITY; REVIEW; SKIN PHOTOSENSITIVITY; STRESS; VIRUS INFECTION;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; PERYLENE; PHOTOCHEMOTHERAPY; PHOTOSENSITIZING AGENTS; SIGNAL TRANSDUCTION;

EID: 84857516853     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712799034842     Document Type: Review

References (95)

1. Karioti, A.; Bilia, A.R. Hypericins as potential leads for new therapeutics. Int J Mol Sci, 2010, 11(2), 562-594.
2. Shen, L.; Ji, H.F.; Zhang, H.Y. Anion of hypericin is crucial to understanding the photosensitive features of the pigment. Bioorg Med Chem Lett, 2006, 16(5), 1414-1417. (Pubitemid 43143033)
3. Das, K.; Smirnov, A.V.; Wen, J.; Miskovsky, P.; Petrich, J.W. Photophysics of hypericin and hypocrellin A in complex with subcellular components: Interactions with human serum albumin. Photochem Photobiol, 1999, 69(6), 633-645. (Pubitemid 129548821)
4. Showalter, B.M.; Datta, A.; Chowdhury, P.K.; Park, J.; Bandyopadhyay, P.; Choudhury, P.K., et al. Identification of a vibrational frequency corresponding to H-Atom translocation in hypericin. Photochem Photobiol, 2001, 74(2), 157-163.
5. Theodossiou, T.A.; Papakyriakou, A.; Hothersall, J.S. Molecular modeling and experimental evidence for hypericin as a substrate for mitochondrial complex III; mitochondrial photodamage as demonstrated using specific inhibitors. Free Radic Biol Med, 2008, 45(11), 1581-1590.
6. Thomas, C.; Pardini, R.S. Oxygen dependence of hypericin-induced phototoxicity to EMT6 mouse mammary carcinoma cells. Photochem Photobiol, 1992, 55(6), 831-837.
7. Ali, S.M.; Olivo, M. Nitric oxide mediated photo-induced cell death in human malignant cells. Int J Oncol, 2003, 22(4), 751-756.
8. Du, H.Y.; Olivo, M.; Tan, B.K.; Bay, B.H. Hypericin-mediated photodynamic therapy induces lipid peroxidation and necrosis in nasopharyngeal cancer. Int J Oncol, 2003, 23(5), 1401-1405.
9. Buriankova, L.; Buzova, D.; Chorvat, D., Jr.; Sureau, F.; Brault, D.; Miskovsky, P., et al. Kinetics of hypericin association with low-density lipoproteins. Photochem Photobiol, 2011, 87(1), 56-63.
10. Miskovsky, P.; Jancura, D.; Sanchez-Cortes, S.; Kocisova, E.; Chinsky, L. Antiretrovirally Active Drug Hypericin Binds the IIA Subdomain of Human Serum Albumin: Resonance Raman and Surface-Enhanced Raman Spectroscopy Study. Journal of the American Chemical Society, 1998, 120(25), 6374-6379. (Pubitemid 28346411)
11. Miskovsky, P. Hypericin-A new antiviral and antitumor photosensitizer: Mechanism of action and interaction with biological macromolecules. Curr Drug Targets, 2002, 3(1), 55-84. (Pubitemid 34296305)
12. Roelants, M.; Van Cleynenbreugel, B.; Lerut, E.; Van Poppel, H.; de Witte, P.A. 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, 2011, 10(1), 151-159.
13. Kubin, A.; Loew, H.G.; Burner, U.; Jessner, G.; Kolbabek, H.; Wierrani, F. How to make hypericin water-soluble. Pharmazie, 2008, 63(4), 263-269. (Pubitemid 351543023)
14. Derycke, A.S.; De Witte, P.A. Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes. Int J Oncol, 2002, 20(1), 181-187.
15. Zeisser-Labouebe, M.; Delie, F.; Gurny, R.; Lange, N. Benefits of nanoencapsulation for the hypercin-mediated photodetection of ovarian micrometastases. Eur J Pharm Biopharm, 2009, 71(2), 207-213.
16. Huygens, A.; Kamuhabwa, A.R.; Roskams, T.; B, V.A.N.C.; H, V.A.N.P.; de Witte, P.A. 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. (Pubitemid 40825674)
17. Huygens, A.; Crnolatac, I.; Develter, J.; Van Cleynenbreugel, B.; Van der Kwast, T.; de Witte, P.A. Differential accumulation of hypericin in spheroids composed of T-24 transitional cell carcinoma cells expressing different levels of E-cadherin. J Urol, 2008, 179(5), 2014-2019.
18. Sattler, S.; Schaefer, U.; Schneider, W.; Hoelzl, J.; Lehr, C.M. Binding, uptake, and transport of hypericin by Caco-2 cell monolayers. J Pharm Sci, 1997, 86(10), 1120-1126. (Pubitemid 27430916)
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), 921-939.
20. Ali, S.M.; Olivo, M. Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. Int J Oncol, 2002, 21(3), 531-540.
21. Agostinis, P.; Vantieghem, A.; Merlevede, W.; de Witte, P.A. Hypericin in cancer treatment: More light on the way. Int J Biochem Cell Biol, 2002, 34(3), 221-241. (Pubitemid 34159138)
22. Miskovsky, P.; Sureau, F.; Chinsky, L.; Turpin, P.Y. Subcellular distribution of hypericin in human cancer cells. Photochem Photobiol, 1995, 62(3), 546-549.
23. Okpanyi, S.N.; Lidzba, H.; Scholl, B.C.; Miltenburger, H.G. [Genotoxicity of a standardized Hypericum extract]. Arzneimittelforschung, 1990, 40(8), 851-855.
24. Miskovsky, P.; Chinsky, L.; Wheeler, G.V.; Turpin, P.Y. Hypericin site specific interactions within polynucleotides used as DNA model compounds. J Biomol Struct Dyn, 1995, 13(3), 547-552. (Pubitemid 26013704)
25. Sanchez-Cortes, S.; Miskovsky, P.; Jancura, D.; Bertoluzza, A. Specific Interactions of Antiretroviraly Active Drug Hypericin with DNA As Studied by Surface-Enhanced Resonance Raman Spectroscopy. The Journal of Physical Chemistry, 1996, 100(5), 1938-1944. (Pubitemid 126790018)
26. Huntosova, V.; Alvarez, L.; Bryndzova, L.; Nadova, Z.; Jancura, D.; Buriankova, L., et al. Interaction dynamics of hypericin with low-density lipoproteins and U87-MG cells. Int J Pharm, 2010, 389(1-2), 32-40.
27. Kubin, A.; Wierrani, F.; Burner, U.; Alth, G.; Grunberger, W. Hypericin-The facts about a controversial agent. Curr Pharm Des, 2005, 11(2), 233-253.
28. Blank, M.; Mandel, M.; Hazan, S.; Keisari, Y.; Lavie, G. Anti-cancer activities of hypericin in the dark. Photochem Photobiol, 2001, 74(2), 120-125.
29. Siboni, G.; Amit-Patito, I.; Weizman, E.; Waintraub-Porat, M.; Weitman, H.; Ehrenberg, B., et al. Specificity of photosensitizer accumulation in undifferentiated versus differentiated colon carcinoma cells. Cancer Lett, 2003, 196(1), 57-64. (Pubitemid 36830911)
30. Blank, M.; Lavie, G.; Mandel, M.; Hazan, S.; Orenstein, A.; Meruelo, D., et al. Antimetastatic activity of the photodynamic agent hypericin in the dark. Int J Cancer, 2004, 111(4), 596-603. (Pubitemid 39045328)
31. Muldner, H.; Zoller, M. [Antidepressive effect of a Hypericum extract standardized to an active hypericine complex. Biochemical and clinical studies]. Arzneimittelforschung, 1984, 34(8), 918-920. (Pubitemid 14099922)
32. Raffa, R.B. Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals sigma receptor binding. Life Sci, 1998, 62(16), PL265-270. (Pubitemid 28143989)
33. Tang, J.; Colacino, J.M.; Larsen, S.H.; Spitzer, W. Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses. Antiviral Res, 1990, 13(6), 313-325. (Pubitemid 20223545)
34. Lavie, G.; Valentine, F.; Levin, B.; Mazur, Y.; Gallo, G.; Lavie, D., et al. Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. Proc Natl Acad Sci U S A, 1989, 86(15), 5963-5967. (Pubitemid 19217568)
35. Kuhn, D. Hypericin: An answer for safer blood? Common Factor, 1995, (no 10), 36.
36. Hudson, J.B.; Lopez-Bazzocchi, I.; Towers, G.H. Antiviral activities of hypericin. Antiviral Res, 1991, 15(2), 101-112.
37. Hudson, J.B.; Harris, L.; Towers, G.H. The importance of light in the anti-HIV effect of hypericin. Antiviral Res, 1993, 20(2), 173-178. (Pubitemid 23024882)
38. Kraus, G.A.; Pratt, D.; Tossberg, J.; Carpenter, S. Antiretroviral activity of synthetic hypericin and related analogs. Biochem Biophys Res Commun, 1990, 172(1), 149-153. (Pubitemid 20352512)
39. Agostinis, P.; Berg, K.; Cengel, K.A.; Foster, T.H.; Girotti, A.W.; Gollnick, S.O., et al. Photodynamic therapy of cancer: An update. CA Cancer J Clin, 2011, 61(4), 250-281.
40. Vandepitte, J.; Van Cleynenbreugel, B.; Hettinger, K.; Van Poppel, H.; de Witte, P.A. Biodistribution of PVP-hypericin and hexaminolevulinateinduced PpIX in normal and orthotopic tumor-bearing rat urinary bladder. Cancer Chemother Pharmacol, 2011, 67(4), 775-781.
41. Diwu, Z.; Lown, J.W. Photosensitization with anticancer agents. 17. EPR studies of photodynamic action of hypericin: Formation of semiquinone radical and activated oxygen species on illumination. Free Radic Biol Med, 1993, 14(2), 209-215. (Pubitemid 23037077)
42. Berlanda, J.; Kiesslich, T.; Engelhardt, V.; Krammer, B.; Plaetzer, K. Comparative in vitro study on the characteristics of different photosensitizers employed in PDT. J Photochem Photobiol B, 2010, 100(3), 173-180.
43. Kamuhabwa, A.R.; Agostinis, P.; D'Hallewin, M.A.; Kasran, A.; de Witte, P.A. Photodynamic activity of hypericin in human urinary bladder carcinoma cells. Anticancer Res, 2000, 20(4), 2579-2584. (Pubitemid 30614470)
44. Chen, B.; Roskams, T.; Xu, Y.; Agostinis, P.; de Witte, P.A. Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model. Int J Cancer, 2002, 98(2), 284-290. (Pubitemid 34150815)
45. Chen, B.; Zupko, I.; de Witte, P.A. Photodynamic therapy with hypericin in a mouse P388 tumor model: Vascular effects determine the efficacy. Int J Oncol, 2001, 18(4), 737-742.
46. Chen, B.; Xu, Y.; Roskams, T.; Delaey, E.; Agostinis, P.; Vandenheede, J.R., et al. Efficacy of antitumoral photodynamic therapy with hypericin: Relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model. Int J Cancer, 2001, 93(2), 275-282. (Pubitemid 32574285)
47. Sanovic, R.; Verwanger, T.; Hartl, A.; Krammer, B. Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma. Photodiagnosis Photodyn Ther, 2011, 8(4), 291-6.
48. Chen, B.; Roskams, T.; de Witte, P.A. Antivascular tumor eradication by hypericin-mediated photodynamic therapy. Photochem Photobiol, 2002, 76(5), 509-513.
49. Krammer, B. Vascular effects of photodynamic therapy. Anticancer Res, 2001, 21(6B), 4271-4277. (Pubitemid 34245368)
50. Engelhardt, V.; Krammer, B.; Plaetzer, K. Antibacterial photodynamic therapy using water-soluble formulations of hypericin or mTHPC is effective in inactivation of Staphylococcus aureus. Photochem Photobiol Sci, 2010, 9(3), 365-369.
51. Johnson, S.A.; Pardini, R.S. Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells. Free Radic Biol Med, 1998, 24(5), 817-826. (Pubitemid 28169569)
52. Utsumi, T.; Okuma, M.; Utsumi, T.; Kanno, T.; Yasuda, T.; Kobuchi, H., et al. Light-dependent inhibition of protein kinase C and superoxide generation of neutrophils by hypericin, an antiretroviral agent. Arch Biochem Biophys, 1995, 316(1), 493-497.
53. Takahashi, I.; Nakanishi, S.; Kobayashi, E.; Nakano, H.; Suzuki, K.; Tamaoki, T. Hypericin and pseudohypericin specifically inhibit protein kinase C: Possible relation to their antiretroviral activity. Biochem Biophys Res Commun, 1989, 165(3), 1207-1212. (Pubitemid 20029836)
54. Zhang, W.; Law, R.E.; Hinton, D.R.; Couldwell, W.T. Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. Cancer Lett, 1997, 120(1), 31-38. (Pubitemid 27483308)
55. Martinez-Poveda, B.; Quesada, A.R.; Medina, M.A. Hypericin in the dark inhibits key steps of angiogenesis in vitro. Eur J Pharmacol, 2005, 516(2), 97-103. (Pubitemid 40799344)
56. Ali, A.S.; Ali, S.; El-Rayes, B.F.; Philip, P.A.; Sarkar, F.H. Exploitation of protein kinase C: A useful target for cancer therapy. Cancer Treat Rev, 2009, 35(1), 1-8.
57. de Witte, P.; Agostinis, P.; Van Lint, J.; Merlevede, W.; Vandenheede, J.R. Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin. Biochem Pharmacol, 1993, 46(11), 1929-1936. (Pubitemid 23361898)
58. Hwang, M.S.; Yum, Y.N.; Joo, J.H.; Kim, S.; Lee, K.K.; Gee, S.W., et al. Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin. Anticancer Res, 2001, 21(4A), 2649-2655. (Pubitemid 33054436)
59. Pajonk, F.; Scholber, J.; Fiebich, B. Hypericin-An inhibitor of proteasome function. Cancer Chemother Pharmacol, 2005, 55(5), 439-446.
60. Woo, J.H.; Li, D.; Wilsbach, K.; Orita, H.; Coulter, J.; Tully, E., et al. Coix seed extract, a commonly used treatment for cancer in China, inhibits NFkappaB and protein kinase C signaling. Cancer Biol Ther, 2007, 6(12), 2005-2011. (Pubitemid 351590416)
61. Bork, P.M.; Bacher, S.; Schmitz, M.L.; Kaspers, U.; Heinrich, M. Hypericin as a non-Antioxidant inhibitor of NF-kappa B. Planta Med, 1999, 65(4), 297-300.
62. Chang, Y.; Wang, S.J. Hypericin, the active component of St. John's wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitogen-Activated protein kinase-dependent pathway. Eur J Pharmacol, 2010, 634(1-3), 53-61.
63. Butterweck, V. Mechanism of action of St John's wort in depression : What is known? CNS Drugs, 2003, 17(8), 539-562. (Pubitemid 36774135)
64. Kang, B.Y.; Chung, S.W.; Kim, T.S. Inhibition of interleukin-12 production in lipopolysaccharide-Activated mouse macrophages by hpyericin, an active component of Hypericum perforatum. Planta Med, 2001, 67(4), 364-366. (Pubitemid 32588577)
65. Guler, R.; Afshar, M.; Arendse, B.; Parihar, S.P.; Revaz-Breton, M.; Leitges, M., et al. PKCdelta regulates IL-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis. Eur J Immunol, 2011, 41(3), 706-715.
66. Tada, H.; Kuboki, K.; Nomura, K.; Inokuchi, T. High glucose levels enhance TGF-beta1-thrombospondin-1 pathway in cultured human mesangial cells via mechanisms dependent on glucose-induced PKC activation. J Diabetes Complications, 2001, 15(4), 193-197. (Pubitemid 33714179)
67. Du, H.Y.; Olivo, M.; Tan, B.K.; Bay, B.H. Photoactivation of hypericin down-regulates glutathione S-transferase activity in nasopharyngeal cancer cells. Cancer Lett, 2004, 207(2), 175-181. (Pubitemid 38457038)
68. Vantieghem, A.; Xu, Y.; Assefa, Z.; Piette, J.; Vandenheede, J.R.; Merlevede, W., et al. Phosphorylation of Bcl-2 in G2/M phase-Arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis. J Biol Chem, 2002, 277(40), 37718-37731.
69. Hendrickx, N.; Volanti, C.; Moens, U.; Seternes, O.M.; de Witte, P.; Vandenheede, J.R., et al. Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem, 2003, 278(52), 52231-52239. (Pubitemid 38035811)
70. Assefa, Z.; Vantieghem, A.; Declercq, W.; Vandenabeele, P.; Vandenheede, J.R.; Merlevede, W., et al. The activation of the c-Jun N-terminal kinase and p38 mitogen-Activated protein kinase signaling pathways protects HeLa cells from apoptosis following photodynamic therapy with hypericin. J Biol Chem, 1999, 274(13), 8788-8796. (Pubitemid 29164677)
71. Buytaert, E.; Matroule, J.Y.; Durinck, S.; Close, P.; Kocanova, S.; Vandenheede, J.R., et al. Molecular effectors and modulators of hypericinmediated cell death in bladder cancer cells. Oncogene, 2008, 27(13), 1916-1929. (Pubitemid 351430819)
72. Kocanova, S.; Buytaert, E.; Matroule, J.Y.; Piette, J.; Golab, J.; de Witte, P., et al. Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy. Apoptosis, 2007, 12(4), 731-741. (Pubitemid 46411467)
73. Varriale, L.; Coppola, E.; Quarto, M.; Veneziani, B.M.; Palumbo, G. Molecular aspects of photodynamic therapy: Low energy pre-sensitization of hypericin-loaded human endometrial carcinoma cells enhances phototolerance, alters gene expression and affects the cell cycle. FEBS Lett, 2002, 512(1-3), 287-290. (Pubitemid 34164496)
74. Miccoli, L.; Beurdeley-Thomas, A.; De Pinieux, G.; Sureau, F.; Oudard, S.; Dutrillaux, B., et al. Light-induced photoactivation of hypericin affects the energy metabolism of human glioma cells by inhibiting hexokinase bound to mitochondria. Cancer Res, 1998, 58(24), 5777-5786. (Pubitemid 29006419)
75. Ali, S.M.; Chee, S.K.; Yuen, G.Y.; Olivo, M. Hypocrellins and Hypericin induced apoptosis in human tumor cells: A possible role of hydrogen peroxide. Int J Mol Med, 2002, 9(5), 461-472.
76. Buytaert, E.; Callewaert, G.; Hendrickx, N.; Scorrano, L.; Hartmann, D.; Missiaen, L., 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(6), 756-758. (Pubitemid 46671205)
77. Skulachev, V.P. The programmed death phenomena, aging, and the Samurai law of biology. Exp Gerontol, 2001, 36(7), 995-1024. (Pubitemid 32515217)
78. Berlanda, J.; Kiesslich, T.; Oberdanner, C.B.; Obermair, F.J.; Krammer, B.; Plaetzer, K. Characterization of apoptosis induced by photodynamic treatment with hypericin in A431 human epidermoid carcinoma cells. J Environ Pathol Toxicol Oncol, 2006, 25(1-2), 173-188. (Pubitemid 43341239)
79. Hendrickx, N.; Dewaele, M.; Buytaert, E.; Marsboom, G.; Janssens, S.; Van Boven, M., et al. Targeted inhibition of p38alpha MAPK suppresses tumorassociated endothelial cell migration in response to hypericin-based photodynamic therapy. Biochem Biophys Res Commun, 2005, 337(3), 928-935. (Pubitemid 41447003)
80. Sackova, V.; Fedorocko, P.; Szilardiova, B.; Mikes, J.; Kleban, J. Hypericininduced photocytotoxicity is connected with G2/M arrest in HT-29 and Sphase arrest in U937 cells. Photochem Photobiol, 2006, 82(5), 1285-1291. (Pubitemid 44702010)
81. Vantieghem, A.; Xu, Y.; Declercq, W.; Vandenabeele, P.; Denecker, G.; Vandenheede, J.R., et al. Different pathways mediate cytochrome c release after photodynamic therapy with hypericin. Photochem Photobiol, 2001, 74(2), 133-142.
82. Weller, M.; Trepel, M.; Grimmel, C.; Schabet, M.; Bremen, D.; Krajewski, S., et al. Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wildtype p53. Neurol Res, 1997, 19(5), 459-470. (Pubitemid 27419416)
83. Sarissky, M.; Lavicka, J.; Kocanova, S.; Sulla, I.; Mirossay, A.; Miskovsky, P., et al. Diazepam enhances hypericin-induced photocytotoxicity and apoptosis in human glioblastoma cells. Neoplasma, 2005, 52(4), 352-359. (Pubitemid 41076205)
84. Vitale, I.; Antoccia, A.; Crateri, P.; Leone, S.; Arancia, G.; Tanzarella, C. Caspase-independent apoptosis is activated by diazepam-induced mitotic failure in HeLa cells, but not in human primary fibroblasts. Apoptosis, 2005, 10(4), 909-920. (Pubitemid 41187088)
85. Koval, J.; Mikes, J.; Jendzelovsky, R.; Kello, M.; Solar, P.; Fedorocko, P. Degradation of HER2 receptor through hypericin-mediated photodynamic therapy. Photochem Photobiol, 2010, 86(1), 200-205.
86. Schempp, C.M.; Simon-Haarhaus, B.; Termeer, C.C.; Simon, J.C. Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8. FEBS Lett, 2001, 493(1), 26-30. (Pubitemid 32241170)
87. Ali, S.M.; Chee, S.K.; Yuen, G.Y.; Olivo, M. Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells. Int J Mol Med, 2002, 9(6), 601-616.
88. Du, H.; Olivo, M.; Mahendran, R.; Bay, B.H. Modulation of Matrix metalloproteinase-1 in nasopharyngeal cancer cells by photoactivation of hypericin. Int J Oncol, 2004, 24(3), 657-662.
89. Du, H.Y.; Olivo, M.; Mahendran, R.; Huang, Q.; Shen, H.M.; Ong, C.N., et al. Hypericin photoactivation triggers down-regulation of matrix metalloproteinase-9 expression in well-differentiated human nasopharyngeal cancer cells. Cell Mol Life Sci, 2007, 64(7-8), 979-988. (Pubitemid 46597767)
90. Staples, C.J.; Owens, D.M.; Maier, J.V.; Cato, A.C.; Keyse, S.M. Cross-talk between the p38alpha and JNK MAPK pathways mediated by MAP kinase phosphatase-1 determines cellular sensitivity to UV radiation. J Biol Chem, 2010, 285(34), 25928-25940.
91. Bhuvaneswari, R.; Gan, Y.Y.; Yee, K.K.; Soo, K.C.; Olivo, M. Effect of hypericin-mediated photodynamic therapy on the expression of vascular endothelial growth factor in human nasopharyngeal carcinoma. Int J Mol Med, 2007, 20(4), 421-428.
92. Bhuvaneswari, R.; Gan, Y.Y.; Lucky, S.S.; Chin, W.W.; Ali, S.M.; Soo, K.C., et al. Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy. Mol Cancer, 2008, 7(56.
93. Du, H.; Bay, B.H.; Mahendran, R.; Olivo, M. Hypericin-mediated photodynamic therapy elicits differential interleukin-6 response in nasopharyngeal cancer. Cancer Lett, 2006, 235(2), 202-208.
94. Buytaert, E.; Callewaert, G.; Vandenheede, J.R.; Agostinis, P. Deficiency in apoptotic effectors Bax and Bak reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum. Autophagy, 2006, 2(3), 238-240. (Pubitemid 44030895)
95. Blank, M.; Mandel, M.; Keisari, Y.; Meruelo, D.; Lavie, G. Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for mitotic cell death in cancer cells induced with hypericin. Cancer Res, 2003, 63(23), 8241-8247. (Pubitemid 37549474)