PMID- 22360555
OWN - NLM
STAT- MEDLINE
DCOM- 20120730
LR  - 20211203
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 18
IP  - 10
DP  - 2012
TI  - Translational research of photodynamic therapy with acridine orange which targets 
      cancer acidity.
PG  - 1414-20
AB  - During the past 20 years, we have found that acridine orange (AO) selectively 
      accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal 
      effects against sarcoma cells in vitro after illumination of the tumor cells with 
      visible light or irradiation of the cells with low-dose X-rays. Based on the data 
      obtained from basic research, we have employed reduction surgery followed by 
      photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with 
      musculoskeletal sarcomas, in an attempt to maintain excellent limb function in 
      the patients. We have obtained good local control rates and remarkably better 
      limb functions with this approach as compared to the results obtained with the 
      conventional wide resection surgery. Our basic research demonstrated that AO 
      accumulates densely in intracellular acidic vesicles, especially lysosomes, in an 
      acidity-dependent manner. In cancer cells that proliferate under hypoxic 
      conditions or with Warburg's effect, active glycolysis produces an enormous 
      number of protons, which are released by the cells via proton pumps into the 
      extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid. 
      Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO 
      shows marked and prolonged accumulation in the acidic lysosomes of cancer cells. 
      Photon energy excites the AO resulting in the production of activated oxygen 
      species, which oxidize the fatty acids of the lysosomal membrane, resulting in 
      the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer 
      cells. Based on these observations, we conclude that AO-PDT & RDT target acidic 
      vesicles, especially the lysosomes, in cancer cells, to exhibit selective 
      anti-cancer cell activity. Therefore, it is suggested that AO excited by photon 
      energy has excellent potential as an anticancer "Magic Bullet".
FAU - Kusuzaki, Katsuyuki
AU  - Kusuzaki K
AD  - Department of Molecular Cell Physiology, Kyoto Prefectural University of 
      Medicine, Graduate School of Medical Science, Kawaramachi Hirokoji Kajiicho 465, 
      Kamigyo-ku Kyoto 602-8566, Japan. kusuzaki@kpu-m.ac.jp
FAU - Hosogi, Shigekuni
AU  - Hosogi S
FAU - Ashihara, Eishi
AU  - Ashihara E
FAU - Matsubara, Takao
AU  - Matsubara T
FAU - Satonaka, Haruhiko
AU  - Satonaka H
FAU - Nakamura, Tomoki
AU  - Nakamura T
FAU - Matsumine, Akihiko
AU  - Matsumine A
FAU - Sudo, Akihiro
AU  - Sudo A
FAU - Uchida, Atsumasa
AU  - Uchida A
FAU - Murata, Hiroaki
AU  - Murata H
FAU - Baldini, Nicola
AU  - Baldini N
FAU - Fais, Stefano
AU  - Fais S
FAU - Marunaka, Yoshinori
AU  - Marunaka Y
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acid-Base Equilibrium/*drug effects
MH  - Acridine Orange/chemistry/*pharmacology
MH  - Animals
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Mice
MH  - Molecular Structure
MH  - *Photochemotherapy
MH  - Sarcoma/*drug therapy
MH  - Translational Research, Biomedical
EDAT- 2012/03/01 06:00
MHDA- 2012/07/31 06:00
CRDT- 2012/02/25 06:00
PHST- 2011/11/30 00:00 [received]
PHST- 2011/12/26 00:00 [accepted]
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/07/31 06:00 [medline]
AID - CPD-EPUB-20120223-005 [pii]
AID - 10.2174/138161212799504812 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2012;18(10):1414-20. doi: 10.2174/138161212799504812.