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Mild Heat Shock Induces Autophagic
Growth Arrest, But Not Apoptosis in U251-MG and U87-MG Human Malignant Glioma
Cells
Tadashi Komata, Takao Kanzawa, Takeo Nashimoto, Hiroshi
Aoki, Shin Endo, Masaaki Nameta, Hideaki Takahashi, Tadashi Yamamoto, Seiji Kondo,
Ryuichi Tanaka
Department
of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan (T.Ko.,
T.N., H.A., S.E., H.T., R.T.); Department of Neurosurgery, Brain Research Institute,
Niigata University, Niigata, Japan & Department of Neurosurgery, The
University of Texas, MD Anderson Cancer Center, Houston, TX, USA (T.Ka.);
Electron Microscope Laboratory, Niigata University, Niigata, Japan (M.N., T.Y.);
Department of Neurosurgery, The University of Texas, MD Anderson Cancer Center,
Houston, TX, USA (S.K.).
Although hyperthermia has been used as a treatment of malignant brain
tumors, it is not yet clear what is the mechanism of the cell growth inhibition
by heat shock, especially by the temperature which has clinically been applied
to tumor–brain border-zone, 42–43°C.
Therefore, we evaluated the change of U251-MG and U87-MG human malignant glioma
cells after 43°C-heat shock comparing with that
of 45°C.
First, we observed that cell growth was transiently inhibited after 43°C-heat
shock for 3 or 5 days, in U251-MG or U87-MG cells, respectively, which was
followed by regrowth.
During the period of transient growth inhibition, mild G2/M arrest was
observed.
However, apoptosis was observed in only 2.7% or 1.5%, of 43°C-heated
cells, in U251-MG or U87-MG cells, respectively.
Instead, transmission electron micrography showed the formation of vacuoles,
degeneration of mitochondria, and autophagosomes.
Moreover, in the both cell lines, flow-cytometric analysis with acridine orange
revealed the induction of acidic vesicle organelles, which was blocked by
3-methyladenine (3-MA), suggesting the involvement of autophagy.
Furthermore, while 3-MA did not increase the anti-tumor effect of 43°C-heat
shock, bafilomycin A1, another autophagy inhibitor, did significantly enhance
the effect in U251-MG cells.
Taken together, mild heat shock (43°C for 2
h) causes autophagy and mild G2/M arrest, but does not induce apparent
apoptosis in U251-MG and U87-MG glioma cells.
Inhibition of autophagy with bafilomycin A1 may increase the anti-tumor efficacy
of mild heat shock against some malignant glioma cells.
Keywords:
apoptosis, autophagy, cell cycle arrest, electron micrography, glioma,
hyperthermia
Copyright ©
2004 Kluwer Academic Publishers.
All rights reserved
Source: http://journals.kluweronline.com/article.asp?PIPS=5268438
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