PMID- 11278320
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 18
DP  - 2001 May 4
TI  - Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. 
      Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy 
      apoptosis.
PG  - 15481-8
AB  - Photodynamic therapy (PDT), a promising treatment modality, is an oxidative 
      stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. 
      Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its 
      therapeutic efficacy. Although studies suggest the involvement of multiple 
      pathways, the triggering event(s) responsible for PDT-mediated apoptotic response 
      is(are) not clear. To investigate the role of Bcl-2 in PDT-mediated apoptosis, we 
      employed Bcl-2-antisense and -overexpression approaches in two cell types 
      differing in their responses toward PDT apoptosis. In the first approach, we 
      treated radiation-induced fibrosarcoma (RIF 1) cells, which are resistant to 
      silicon phthalocyanine (Pc 4)-PDT apoptosis, with Bcl-2-antisense 
      oligonucleotide. This treatment resulted in sensitization of RIF 1 cells to 
      PDT-mediated apoptosis as demonstrated by i) cleavage of poly(ADP-ribose) 
      polymerase, ii) DNA ladder formation, iii) terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and iv) 
      DEVDase activity. This treatment also resulted in oligonucleotide 
      concentration-dependent decrease in cell viability and down-regulation of Bcl-2 
      protein with a concomitant increase in apoptosis. However, the level of Bax, a 
      pro-apoptotic member of Bcl-2 family, remained unaltered. In the second approach, 
      an overexpression of Bcl-2 in PDT apoptosis-sensitive human epidermoid carcinoma 
      (A431) cells resulted in enhanced apoptosis and up-regulation of Bax following 
      PDT. In both the approaches, the increased Bax/Bcl-2 ratio was associated with an 
      increased apoptotic response of PDT. Our data also demonstrated that PDT results 
      in modulation of other Bcl-2 family members in a way that the overall ratio of 
      pro-apoptotic and anti-apoptotic member proteins favors apoptosis.
FAU - Srivastava, M
AU  - Srivastava M
AD  - Department of Dermatology, Case Western Reserve University and Research Institute 
      of University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
FAU - Ahmad, N
AU  - Ahmad N
FAU - Gupta, S
AU  - Gupta S
FAU - Mukhtar, H
AU  - Mukhtar H
LA  - eng
GR  - P01 CA 48735/CA/NCI NIH HHS/United States
GR  - P30 AR 39750/AR/NIAMS NIH HHS/United States
GR  - P30 CA 43703/CA/NCI NIH HHS/United States
GR  - R01 CA 51802/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010131
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BAX protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - *Apoptosis
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Survival
MH  - DNA Primers
MH  - Humans
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - *Photochemotherapy
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*physiology
MH  - Tumor Cells, Cultured
MH  - bcl-2-Associated X Protein
EDAT- 2001/03/30 10:00
MHDA- 2001/06/29 10:01
CRDT- 2001/03/30 10:00
PHST- 2001/03/30 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/03/30 10:00 [entrez]
AID - S0021-9258(19)56852-1 [pii]
AID - 10.1074/jbc.M006920200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 May 4;276(18):15481-8. doi: 10.1074/jbc.M006920200. Epub 2001 
      Jan 31.