[en] Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c. Preincubation of cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-kappaB activation and apoptosis were clearly independent although NF-kappaB was shown to counteract apoptosis mediated by PPME photosensitization.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Matroule, Jean-Yves; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Carthy, Chris M; QLT Inc.
Granville, David J; QLT Inc.
Jolois, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Hunt, David WC; QLT Inc.
Piette, Jacques ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Language :
English
Title :
Mechanism of Colon Cancer Cell Apoptosis Mediated by Pyropheophorbide-a Methylester Photosensitization
Lin C.P., Lynch M.C., Kochevar I.E. Exp. Cell. Res. 2000, 259:351-359.
MacDonald J.J., Morgan J., Bellnier D.A., Paszkiewicz G.M., Whitaker J.E., Litchfield D.J., Dougherty T.J. Photochem. Photobiol. 1999, 70:789-797.
Matroule J.Y., Bonizzi G., Morliere P., Paillous N., Santus R., Bours V., Piette J. J. Biol. Chem. 1999, 274:2988-3000.
Matroule J.Y., Hellin A.C., Morliere P., Fabiano A.S., Santus R., Merville M.P., Piette J. Photochem. Photobiol. 1999, 70:540-548.
Miller G.G., Brown K., Moore R.B., Diwu Z.J., Liu J., Huang L., Lown J.W., Begg D.A., Chlumecky V., Tulip J. Photochem. Photobiol. 1995, 61:632-638.
Monney L., Olivier R., Otter I., Jansen B., Poirier G.G., Borner C. Eur. J. Biochem. 1998, 251:295-303.
Morgan J., Potter W.R., Oseroff A.R. Photochem. Photobiol. 2000, 71:747-757.
Murphree A.L., Villablanca J.G., Deegan III W.F., Sato J.K., Malogolowkin M., Fisher A., Parker R., Reed E., Gomer C.J. Arch. Ophthalmol. 1996, 114:1348-1356.
Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B.A., Yuan J. Nature 2000, 403:98-103.
Oleinick N.L., Evans H.H. Radiat. Res. 1998, 150.
Pandey R.K., Sumlin A.B., Constantine S., Aoudla M., Potter W.R., Bellnier D.A., Henderson B.W., Rodgers M.A., Smith K.M., Dougherty T.J. Photochem. Photobiol. 1996, 64:194-204.
Pass H.I. J. Natl. Cancer Inst. 1993, 85:443-456.
Payne J.T., McCaw D.L., Casteel S.W., Frazier D., Rogers K., Tompson R.V. Lasers Surg. Med. 1996, 18:406-409.
Plumpe J., Malek N.P., Bock C.T., Rakemann T., Manns M.P., Trautwein C. Am. J. Physiol. Gastrointest. Liver Physiol. 2000, 278.
Rivera-Walsh I., Cvijic M.E., Xiao G., Sun S.C. J. Biol. Chem. 2000, 275:25222-25230.
Ruck A., Heckelsmiller K., Kaufmann R., Grossman N., Haseroth E., Akgun N. Photochem. Photobiol. 2000, 72:210-216.
Saleh A., Srinivasula S.M., Acharya S., Fishel R., Alnemri E.S. J. Biol. Chem. 1999, 274:17941-17945.
Schneider P., Tschopp J. Pharm. Acta Helv. 2000, 74:281-286.
Shimizu S., Konishi A., Kodama T., Tsujimoto Y. Proc. Natl. Acad. Sci. USA 2000, 97:3100-3105.
Shimizu S., Narita M., Tsujimoto Y. Nature 1999, 399:483-487.
Shimura M., Osawa Y., Yuo A., Hatake K., Takaku F., Ishizaka Y. J. Leukoc. Biol. 2000, 68:87-96.
Srivastava R.K., Mi Q.S., Hardwick J.M., Longo D.L. Proc. Natl. Acad. Sci. USA 1999, 96:3775-3780.
Steller H. Science 1995, 267:1445-1449.
Stridh H., Kimland M., Jones D.P., Orrenius S., Hampton M.B. FEBS Lett. 1998, 429:351-355.
Tafani M., Schneider T.G., Pastorino J.G., Farber J.L. Am. J. Pathol. 2000, 156:2111-2121.
Tajiri H., Hayakawa A., Matsumoto Y., Yokoyama I., Yoshida S. Cancer Lett. 1998, 128:205-210.
Tao J., Sanghera J.S., Pelech S.L., Wong G., Levy J.G. J. Biol. Chem. 1996, 271:27107-27115.
Van Antwerp D.J., Martin S.J., Kafri T., Green D.R., Verma I.M. Science 1996, 274:787-789.