scholarly journals PU-H71, a novel Hsp90 inhibitor, as a potential cancer-specific sensitizer to carbon-ion beam therapy

2016 ◽  
Vol 57 (5) ◽  
pp. 572-575 ◽  
Author(s):  
Huizi Keiko Li ◽  
Yoshitaka Matsumoto ◽  
Yoshiya Furusawa ◽  
Tadashi Kamada
Keyword(s):  
Protein Expression ◽  
Cell Line ◽  
Ion Irradiation ◽  
Ion Beam ◽  
Hsp90 Inhibitor ◽  
Osteosarcoma Cell ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam ◽  
Recombination Pathway

Abstract PU-H71, a heat shock protein 90 (Hsp90) inhibitor, has yielded therapeutic efficacy in many preclinical models and is currently in clinical trials. Carbon-ion radiotherapy (CIRT) has provided successful tumor control; however, there is still room for improvement, particularly in terms of tumor-specific radiosensitization. The Hsp90 inhibitor PU-H71 has been shown to sensitize tumor cells to X-ray radiation. A murine osteosarcoma cell line (LM8) and a normal human fibroblast cell line (AG01522) were treated with PU-H71 before X-ray, 14- or 50-keV/µm carbon-ion beam (C-ion) irradiation. Cell survival and protein expression were evaluated with colony formation and western blot, respectively. Treatment with PU-H71 alone was shown to be non-toxic to both cell lines; however, PU-H71 was shown to significantly sensitize LM8 cells to not only X-ray, but also to C-ion irradiation, while only a minimal sensitizing effect was observed in AG01522 cells. PU-H71 treatment was found to suppress the protein expression levels of Rad51 and Ku70, which are associated with the homologous recombination pathway and the non-homologous end-joining pathway of double-strand break repair. The findings reported here suggest that PU-H71 could be a promising radiosensitizer for CIRT.

scholarly journals Effects of X-ray and carbon ion beam irradiation on membrane permeability and integrity in Saccharomyces cerevisiae cells

2015 ◽  
Vol 56 (2) ◽  
pp. 294-304 ◽  
Author(s):  
Guozhen Cao ◽  
Miaomiao Zhang ◽  
Jianshun Miao ◽  
Wenjian Li ◽  
Jufang Wang ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Membrane Permeability ◽  
Ion Beam ◽  
Beam Irradiation ◽  
Ion Beam Irradiation ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

The Effects of Heavy Ion Particles on Human Megakaryocytopoiesis and Thrombopoiesis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4156-4156
Author(s):  
Ikuo Kashiwakura ◽  
Kenji Takahashi ◽  
Satoru Monzen ◽  
Kiyomi Eguchi-Kasai ◽  
Tsutomu Toki ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ion Beam ◽  
Heavy Ion ◽  
X Rays ◽  
Dna Double Strand Breaks ◽  
Nuclear Facilities ◽  
Plasma Clot ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

Abstract Heavy ion particles provide unique properties in radiotherapy. However, they have also been shown to pose high risks for both work at nuclear facilities and astronauts participating in space missions. In a previous study, we demonstrated that in radio-sensitive megakaryocyte progenitor cells, namely colony-forming unit megakaryocytes (CFU-Meg), a degree of X-ray-induced damage was prevented by post-treatment with several cytokines. In this study, we analyzed the effects of heavy ion particles on megakaryocytopoiesis and thrombopoiesis. The CD34+ CFU-Meg were isolated from human placental and umbilical cord blood using a magnetic isolation kit and then were exposed to a carbon ion beam (LET=50 KeV/mm). They were cultured in a serum free medium supplemented with a thrombopoietin (TPO) alone or a combination of TPO plus other cytokines including stem cell factor, interleukin-3 (IL-3) and Flt3-ligand. The number of CFU-Meg was calculated by a plasma clot technique. The differentiation into megakaryocytes (CD41+) and the release of platelets (CD42a+) in a liquid culture were both analyzed by flow cytometry. The increase of gamma-H2AX, a marker of DNA double-strand breaks (DSBs) was also detected by flow cytometry. The sensitivity of CFU-Meg to a carbon ion beam was found to be extremely high and could not be lowered by any type of cytokines unlike X-rays. However, treatment with TPO plus IL-3 potentially induced megakaryocytopoiesis and thrombopoiesis at 14 days after the exposure to a carbon ion beam at 2 Gy. The cytokine treatment enhanced the induction of gamma-H2AX in X-ray-irradiated CD34+ CFU-Meg but not in a carbon ion beam-irradiated one. These results show that not only the downregulation of death signals, but also the repair of DSBs was less strongly promoted by cytokines in CFU-Meg exposed to a carbon ion beam than X-rays. Different treatments therefore are required to protect against megakaryocytopoiesis and thrombopoiesis damage by heavy ion particles.

Effects of carbon-ion beam or X-ray irradiation on anti-apoptosis ΔNp73 expression in HeLa cells

Gene ◽  
2013 ◽  
Vol 515 (1) ◽  
pp. 208-213 ◽  
Author(s):  
Cui-Xia Di ◽  
Li-Na Yang ◽  
Hong Zhang ◽  
Li-Zhe An ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Hela Cells ◽  
Ion Beam ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

The Role of XRCC4 in Sensitizing Human Colon Cancer Stem-like Cells to X-ray or Carbon Ion Beam

2012 ◽  
Vol 84 (3) ◽  
pp. S685
Author(s):  
S. Sai ◽  
K. Oonishi ◽  
M. Mori ◽  
T. Kamijo ◽  
S. Yamada ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Ion Beam ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

scholarly journals Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 698
Author(s):  
Eun Ho Kim ◽  
Mi-Sook Kim ◽  
Akihisa Takahashi ◽  
Masao Suzuki ◽  
Guillaume Vares ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Zoledronic Acid ◽  
Cell Cycle Progression ◽  
Ion Beam ◽  
Mapk Signaling ◽  
Beam Irradiation ◽  
Ion Beam Irradiation ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

Osteosarcoma (OSA) is the most common malignant bone tumor in children and adolescents. The overall five-year survival rate for all bone cancers is below 70%; however, when the cancer has spread beyond the bone, it is about 15–30%. Herein, we evaluated the effects of carbon-ion beam irradiation alone or in combination with zoledronic acid (ZOL) on OSA cells. Carbon-ion beam irradiation in combination with ZOL significantly inhibited OSA cell proliferation by arresting cell cycle progression and initiating KHOS and U2OS cell apoptosis, compared to treatments with carbon-ion beam irradiation, X-ray irradiation, and ZOL alone. Moreover, we observed that this combination greatly inhibited OSA cell motility and invasion, accompanied by the suppression of the Pi3K/Akt and MAPK signaling pathways, which are related to cell proliferation and survival, compared to individual treatments with carbon-ion beam or X-ray irradiation, or ZOL. Furthermore, ZOL treatment upregulated microRNA (miR)-29b expression; the combination with a miR-29b mimic further decreased OSA cell viability via activation of the caspase 3 pathway. Thus, ZOL-mediated enhancement of carbon-ion beam radiosensitivity may occur via miR-29b upregulation; co-treatment with the miR-29b mimic further decreased OSA cell survival. These findings suggest that the carbon-ion beam irradiation in combination with ZOL has high potential to increase OSA cell death.

scholarly journals Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115121 ◽  
Author(s):  
Napapat Amornwichet ◽  
Takahiro Oike ◽  
Atsushi Shibata ◽  
Hideaki Ogiwara ◽  
Naoto Tsuchiya ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Ion Beam ◽  
Mitotic Catastrophe ◽  
Beam Irradiation ◽  
Ion Beam Irradiation ◽  
Carbon Ion ◽  
X Ray ◽  
Carbon Ion Beam

scholarly journals Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells

2017 ◽  
Vol 58 (6) ◽  
pp. 765-771 ◽  
Author(s):  
Seong-Joon Park ◽  
Kyu Heo ◽  
Chulwon Choi ◽  
Kwangmo Yang ◽  
Akiko Adachi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Ion Irradiation ◽  
Ion Beam ◽  
Melanoma Cells ◽  
Micro Rna ◽  
Carbon Ion ◽  
X Ray ◽  
Melanoma Cell Lines

Abstract The Lin28/let-7 axis plays an important role in tumor initiation and developmental processes. Lin28B is upregulated in a variety of cancers, and its overexpression enhances cancer cell proliferation and radioresistance through the suppression of let-7 micro RNA expression. In this study, we investigated the role of the Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of cancer stem cell (CSC) populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Consistent with these results, Lin28B overexpression reduced the numbers of γH2A.X foci after X-ray irradiation, whereas carbon ion irradiation had no such effect. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.

scholarly journals Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Atanu Ghorai ◽  
Nitai P. Bhattacharyya ◽  
Asitikantha Sarma ◽  
Utpal Ghosh
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Gamma Radiation ◽  
Ion Beam ◽  
Carbon Ion ◽  
X Ray ◽  
High Let ◽  
Carbon Ion Beam ◽  
Induction Of Apoptosis ◽  
Parp 1

Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both12C and gamma induced G2/M arrest although the12C had greater effect. Unlike the gamma,12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET12C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for12C than gamma.

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