The small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

Hamada, Nobuyuki; Kataoka, Keiko; Sora, Sakura; Hara, Takamitsu; Omura-Minamisawa, Motoko; Funayama, Tomoo; Sakashita, Tetsuya; Nakano, Takashi; Kobayashi, Yasuhiko

doi:10.1016/j.radonc.2008.08.006

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…Conventional broadfield irradiation was conducted using broadbeams as described (Hamada et al, , 2008c. Cell monolayers cultured on 60-mm dishes were exposed to three different types of heavy ions (properties listed in Table 2).…”

Section: Heavy-ion Irradiationmentioning

confidence: 99%

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

et al. 2008

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Significant evidence indicates that ionizing radiation causes biological effects in nonirradiated bystander cells having received signals from directly irradiated cells. There is little information available hitherto as to the bystander effect of energetic heavy ions; however, our previous work has shown that in confluent cultures of normal human fibroblast AG01522 cells, targeted exposure of 0.0003% of cells to microbeams of 18.3 MeV/u 12 C (103 keV/µm) and 13.0 MeV/u 20 Ne (375 keV/µm) ions can similarly cause almost 10% decreases in the clonogenic survival, and twofold increments in the incidence of apoptosis whose temporal kinetics varies between irradiated and bystander cells. Using this experimental system, here we further report that bystander responses of AG01522 cells to 17.5 MeV/u 20 Ne ions (294 keV/µm) are consistent with those to 18.3 MeV/u 12 C and 13.0 MeV/u 20 Ne ions. We also demonstrate that such bystander-induced reductions in the survival are less pronounced and occur independently of Bcl-2 overexpression in human cervical cancer HeLa cells.

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Section: Heavy-ion Irradiationmentioning

confidence: 99%

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

et al. 2008

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“…Cells at passage 9 were seeded at 200 cells/cm 2 on 6-cm dishes, and incubated at 37˚C in a humidified atmosphere of 5% CO 2 in air, at which time irradiation was carried out at room temperature as mentioned (Hamada et al, 2008b(Hamada et al, , 2008c(Hamada et al, , 2008d. In brief, cells were exposed to 60 Co γ-rays (0.2 keV/µm) at a dose rate of 1 Gy/min.…”

Section: Cell Culture and Irradiationmentioning

confidence: 99%

Exposure of Normal Human Fibroblasts to Heavy-Ion Radiation Promotes Their Morphological Differentiation

et al. 2008

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Here we investigated the potential impact of energetic heavy ions on fibroblast differentiation. The differentiation pattern was morphologically determined at days 3 and 5 after exposure to graded dose of γ-rays (0.2 keV/µm) or carbon ions (18.3 MeV/u, 108 keV/µm). The cells irradiated with higher doses progressed toward later differentiation stages as time goes postirradiation, but underwent fewer cell divisions. Thus, radiation exposure accelerated morphological differentiation, for which carbon ions were more effective than γ-rays. The relative biological effectiveness of carbon ions for differentiation was higher than that for the clonogenic survival, and this was the most case for terminally differentiated cells that may not divide any more. The results are suggestive of the distinct mechanism underlying inactivation of clonogenic potential between the radiation quality, such that the contribution of the differentiation to heavy ion-induced reductions in the survival is greater than to those induced by photons. Such accelerated differentiation could be a protective mechanism that minimizes further expansion of aberrant cells.

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“…Cell survival was determined using the clonogenic survival assay as described elsewhere (Hamada et al, 2006(Hamada et al, , 2008c(Hamada et al, , 2008d. Briefly, confluent cultures were reinoculated within 1 h postirradiation into 100-mm tissue culture dishes (3020-100, Iwaki) in quadruplicate, and were incubated for 12-13 days, at which time they were fixed in methanol and stained with crystal violet.…”

Section: Cell Survival Analysismentioning

confidence: 99%

A LET-Dependent Decrease in the Apoptotic Response of Normal Human Fibroblast Cultures to Isosurvival Doses of γ-Rays and Energetic Heavy Ions

Hamada

Funayama

et al. 2008

Biol. Sci. Space

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Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. Plentiful evidence has been presented demonstrating that at physically equivalent doses, high-LET energetic heavy ions are more cytotoxic and genotoxic than low-LET photons like X-rays and γ-rays. Notwithstanding, its potential impact at isosurvival doses is yet to be characterized. Here we investigated the cell-killing effectiveness of γ-rays (0.2 keV/µm) and five different beams of heavy ions with LET ranging from 16.2 to 1610 keV/µm in confluent cultures of normal human fibroblasts. The relative biological effectiveness based on the dose giving 10% clonogenic survival peaked at 108 keV/µm. In cultures exposed to the 10% survival doses, the yield of apoptotic cells escalated with time postirradiation but declined with LET. Our results imply that the cell death mode differs with LET at isosurvival levels.

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The small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

Cited by 11 publications

References 24 publications

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

Exposure of Normal Human Fibroblasts to Heavy-Ion Radiation Promotes Their Morphological Differentiation

A LET-Dependent Decrease in the Apoptotic Response of Normal Human Fibroblast Cultures to Isosurvival Doses of γ-Rays and Energetic Heavy Ions

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