Reactive oxygen species and nitric oxide regulate mitochondria-dependent apoptosis and autophagy in evodiamine-treated human cervix carcinoma HeLa cells.
The redox environment of the cell is currently thought to be extremely important to control either apoptosis or autophagy. This study reported that reactive oxygen species (ROS) and nitric oxide (NO) generations were induced by evodiamine time-dependently; while they acted in synergy to trigger mitochondria-dependent apoptosis by induction of mitochondrial membrane permeabilization (MMP) through increasing the Bax/Bcl-2 or Bcl-x(L) ratio. Autophagy was also stimulated by evodiamine, as demonstrated by the positive autophagosome-specific dye monodansylcadaverine (MDC) staining as well as the expressions of autophagy-related proteins, Beclin 1 and LC3. Pre-treatment with 3-MA, the specific inhibitor for autophagy, dose-dependently decreased cell viability, indicating a survival function of autophagy. Importantly, autophagy was found to be promoted or inhibited by ROS/NO in response to the severity of oxidative stress. These findings could help shed light on the complex regulation of intracellular redox status on the balance of autophagy and apoptosis in anti-cancer therapies.
Yang
Jia
J
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Wu
Li-Jun
LJ
Tashino
Shin-Ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000165:Acridine Orange / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009336:Necrosis; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D009569:Nitric Oxide; C049639:evodiamine; D000165:Acridine Orange; C008542:monodansylcadaverine; D002103:Cadaverine