Journal of Pharmacological Sciences (Jan 2004)

Dracorhodin Perchlorate Induces Apoptosis via Activation of Caspases and Generation of Reactive Oxygen Species

  • Mingyu Xia,
  • Dong Wang,
  • Minwei Wang,
  • Shin-ichi Tashiro,
  • Satoshi Onodera,
  • Mutsuhiko Minami,
  • Takashi Ikejima

DOI
https://doi.org/10.1254/jphs.fpj03102x
Journal volume & issue
Vol. 95, no. 2
pp. 273 – 283

Abstract

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Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. The drug induced oligonucleosomal fragmentation of DNA in HeLa cells and increased caspase-3, -8, -9 activities followed by the degradation of caspase-3 substrates, inhibitor of caspase-dependent DNase, and poly-(ADP-ribose) polymerase. It also increased caspase-1 activity and a caspase-1 inhibitor, Ac-YVAD-cmk, and a caspase-10 inhibitor z-AEVD-fmk, also reduced dracorhodinperchlorate-induced HeLa cell death. Dracorhodin perchlorate decreased the expression of anti-apoptotic mitochondrial protein, Bcl-XL, but not Bcl-2; and it increased the expression of pro-apoptotic protein, Bax. Dracorhodin perchlorate induced a sustained generation of reactive oxygen species (ROS) in HeLa cells; caspase-1 inhibitor, Ac-YVAD-cmk, and caspase-3 inhibitor, z-DEVD-fmk, attenuated the generation of ROS. Taken together, our results indicate that dracorhodin perchlorate alters the intracellular redox status, changed the balance of Bcl-XL and Bax protein expression, and induces apoptosis through caspase pathways in HeLa cells. Keywords:: dracorhodin perchlorate, Bax, Bcl-XL, caspase, reactive oxygen species