PMID- 9652788 OWN - NLM STAT- MEDLINE DCOM- 19980710 LR - 20190720 IS - 0304-3835 (Print) IS - 0304-3835 (Linking) VI - 128 IP - 1 DP - 1998 Jun 5 TI - Caspase proteases mediate apoptosis induced by anticancer agent preactivated MC540 in human tumor cell lines. PG - 11-22 AB - The molecular events involved in tumor cell death induced by novel photoproducts of merocyanine 540 (pMC540) are poorly understood. Using HL60 leukemia and M14 melanoma cell lines we investigated the role of the apoptotic pathway in pMC540-mediated cell death. Tumor cells exposed to pMC540 showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced by pMC540 in both tumor cell lines as evidenced by the externalization of phosphatidylserine. A dose-dependent increase in caspase-3 protease activity suppressed by the tetrapeptide inhibitor DEVD-CHO was observed in both cell lines. Western blot analysis of poly (ADP-ribose) polymerase, a caspase substrate, showed the classical cleavage pattern (116 to 89 kDa) associated with apoptosis in pMC540-treated cell lysates. Furthermore, caspase inhibition blocked the externalization of membrane PS, indicating that the loss of membrane phospholipid asymmetry is a downstream event of caspase activation. These findings demonstrate that tumor cell death induced by pMC540 is mediated by caspase proteases. FAU - Pervaiz, S AU - Pervaiz S AD - Department of Physiology, Faculty of Medicine, National University of Singapore, Singapore. shazib@pacific.net.sg FAU - Hirpara, J L AU - Hirpara JL FAU - Clement, M V AU - Clement MV LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (DNA, Neoplasm) RN - 0 (Phosphatidylserines) RN - 0 (Pyrimidinones) RN - 58823-12-4 (merocyanine dye) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - Apoptosis MH - Cell Size MH - Cysteine Endopeptidases/*pharmacology MH - DNA, Neoplasm/analysis MH - Enzyme Activation MH - Humans MH - Leukemia MH - Melanoma MH - Phosphatidylserines/metabolism MH - Pyrimidinones/*pharmacology MH - Tumor Cells, Cultured EDAT- 1998/07/04 00:00 MHDA- 1998/07/04 00:01 CRDT- 1998/07/04 00:00 PHST- 1998/07/04 00:00 [pubmed] PHST- 1998/07/04 00:01 [medline] PHST- 1998/07/04 00:00 [entrez] AID - S0304-3835(98)00021-4 [pii] AID - 10.1016/s0304-3835(98)00021-4 [doi] PST - ppublish SO - Cancer Lett. 1998 Jun 5;128(1):11-22. doi: 10.1016/s0304-3835(98)00021-4.