BAM-SiPc, a novel agent for photodynamic therapy, induces apoptosis in human hepatocarcinoma HepG2 cells by a direct mitochondrial action

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Janice C. Lai
  • Dennis K.P. Ng
  • Wing-Hung Ko
  • Stanley C.H. Leung
  • Kwok-Pui Fung
  • Wing-Ping Fong

Detail(s)

Original languageEnglish
Pages (from-to)413-418
Journal / PublicationCancer Biology and Therapy
Volume5
Issue number4
Publication statusPublished - Apr 2006
Externally publishedYes

Abstract

Photodynamic therapy is recently developed as an effective treatment for malignant disease. The therapeutic effect depends on the properties of the photosensitizers. Among the novel photosensitizers we have synthesized, the unsymmetrical bisamino phthalocyanine, SiPc[C3H5(NMe 2)2O](OMe) (BAM-SiPc) is particularly active in the HepG2 cell culture model. Fluorescence microscopy has also indicated that it targets the mitochondria. In the present investigation, the biochemical mechanisms of BAM-SiPc leading to cell death were investigated. Photodynamic treatment with BAM-SiPc resulted in the generation of reactive oxygen species and a collapse of mitochondrial membrane potential. The pro-apoptotic Bax protein was translocated from the cytosol to mitochondria; while the level of the mitochondrial anti-apoptotic Bcl-2 protein decreased after photodynamic treatment. Cytochrome c, but not apoptosis-inducing factor, was released from the mitochondria into the cytosol, subsequently resulting in the cleavage of poly(ADP-ribose) polymerase. These events were at least partially responsible for the observed BAM-SiPc induced apoptosis, which was clearly demonstrated by (a) the loss of membrane asymmetry, (b) DNA ladder formation, and (c) the presence of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. ©2006 Landes Bioscience.

Research Area(s)

  • Anti-cancer drug, Apoptosis, Mitochondria, Photodynamic therapy, Photosensitizer, Phthalocyanine, Reactive oxygen species

Citation Format(s)

BAM-SiPc, a novel agent for photodynamic therapy, induces apoptosis in human hepatocarcinoma HepG2 cells by a direct mitochondrial action. / Lai, Janice C.; Lo, Pui-Chi; Ng, Dennis K.P.; Ko, Wing-Hung; Leung, Stanley C.H.; Fung, Kwok-Pui; Fong, Wing-Ping.

In: Cancer Biology and Therapy, Vol. 5, No. 4, 04.2006, p. 413-418.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal