Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice

Tadashi Ohara, Tetsuo Morishita, Hidekazu Suzuki, Tatsuhiro Masaoka, Hiromasa Ishii, Toshifumi Hibi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: The effects of bacterial eradication therapy cannot be fully explained simply by elimination of the target bacteria, if one considers the effects of eradication therapy in H. pylori-negative cases of low-grade malignancy MALTomas of the rectum. The present study was undertaken to examine the possibility and mechanism of direct induction of apoptosis of the tumor cells by the antibiotics used for bacterial eradication therapy. Materials and Methods: A B cell lymphoma cell line (300-19) derived from BALB/c mice was co-cultured with amoxicillin or clarithromycin, and amoxicillin and clarithromycin at concentrations equal to or 1/10 × MIC of either drug. Cells cocultured with 1/100 × MIC of the standard anti-tumor agents, adriamycin, vincristine and cyclophosphamide, served as positive controls. Cells cultured without any antibiotic or anti-tumor agent served as controls. In each group, the following analyses were performed: (i) the time-course of changes in the cellular morphology, (ii) the time-course of occurrence of DNA fragmentation, (iii) the appearance of apoptotic changes as evaluated by trypan blue staining, (iv) Bcl-2 expression as examined by immunoblotting, and (v) the expression of TNFR1, Fas, FasL and caspase-3, -8 and -9, as evaluated by immunoblotting. Results: Cells treated with amoxicillin and clarithromycin showed the formation of apoptotic bodies, and degeneration and detachment of the cells in a dose-dependent manner. DNA fragmentation was induced in these cells to a degree similar to that seen in cells treated with the anti-tumor agents. Trypan blue staining also demonstrated apoptosis of the cells and loss of cell viability. Bcl-2 expression was seen only in the control group and FasL was never seen, while the expression of TNFR1, Fas and caspase-3, -8 and -9 was seen in the amoxicillin-treated group, clarithromycin-treated group, amoxicillin and clarithromycin-treated group and the positive control group. Conclusion: Antibiotics used for the eradication of H. pylori can also directly induce apoptosis in mouse B cell lymphoma cells, an action which involves the TNF system.

Original languageEnglish
Pages (from-to)3723-3730
Number of pages8
JournalAnticancer Research
Volume24
Issue number6
Publication statusPublished - 2004 Nov

Fingerprint

B-Cell Lymphoma
Clarithromycin
Apoptosis
Amoxicillin
Anti-Bacterial Agents
Receptors, Tumor Necrosis Factor, Type I
Trypan Blue
Caspase 8
Pylorus
DNA Fragmentation
Neoplasms
Immunoblotting
Caspase 3
Staining and Labeling
Control Groups
Vincristine
Rectum
Doxorubicin
Cyclophosphamide
Cultured Cells

Keywords

  • Apoptosis
  • B cell lymphoma
  • Eradication therapy of H.pylori

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ohara, T., Morishita, T., Suzuki, H., Masaoka, T., Ishii, H., & Hibi, T. (2004). Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice. Anticancer Research, 24(6), 3723-3730.

Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice. / Ohara, Tadashi; Morishita, Tetsuo; Suzuki, Hidekazu; Masaoka, Tatsuhiro; Ishii, Hiromasa; Hibi, Toshifumi.

In: Anticancer Research, Vol. 24, No. 6, 11.2004, p. 3723-3730.

Research output: Contribution to journalArticle

Ohara, T, Morishita, T, Suzuki, H, Masaoka, T, Ishii, H & Hibi, T 2004, 'Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice', Anticancer Research, vol. 24, no. 6, pp. 3723-3730.
Ohara T, Morishita T, Suzuki H, Masaoka T, Ishii H, Hibi T. Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice. Anticancer Research. 2004 Nov;24(6):3723-3730.
Ohara, Tadashi ; Morishita, Tetsuo ; Suzuki, Hidekazu ; Masaoka, Tatsuhiro ; Ishii, Hiromasa ; Hibi, Toshifumi. / Antibiotics directly induce apoptosis in B cell lymphoma cells derived from BALB/c mice. In: Anticancer Research. 2004 ; Vol. 24, No. 6. pp. 3723-3730.
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abstract = "Background: The effects of bacterial eradication therapy cannot be fully explained simply by elimination of the target bacteria, if one considers the effects of eradication therapy in H. pylori-negative cases of low-grade malignancy MALTomas of the rectum. The present study was undertaken to examine the possibility and mechanism of direct induction of apoptosis of the tumor cells by the antibiotics used for bacterial eradication therapy. Materials and Methods: A B cell lymphoma cell line (300-19) derived from BALB/c mice was co-cultured with amoxicillin or clarithromycin, and amoxicillin and clarithromycin at concentrations equal to or 1/10 × MIC of either drug. Cells cocultured with 1/100 × MIC of the standard anti-tumor agents, adriamycin, vincristine and cyclophosphamide, served as positive controls. Cells cultured without any antibiotic or anti-tumor agent served as controls. In each group, the following analyses were performed: (i) the time-course of changes in the cellular morphology, (ii) the time-course of occurrence of DNA fragmentation, (iii) the appearance of apoptotic changes as evaluated by trypan blue staining, (iv) Bcl-2 expression as examined by immunoblotting, and (v) the expression of TNFR1, Fas, FasL and caspase-3, -8 and -9, as evaluated by immunoblotting. Results: Cells treated with amoxicillin and clarithromycin showed the formation of apoptotic bodies, and degeneration and detachment of the cells in a dose-dependent manner. DNA fragmentation was induced in these cells to a degree similar to that seen in cells treated with the anti-tumor agents. Trypan blue staining also demonstrated apoptosis of the cells and loss of cell viability. Bcl-2 expression was seen only in the control group and FasL was never seen, while the expression of TNFR1, Fas and caspase-3, -8 and -9 was seen in the amoxicillin-treated group, clarithromycin-treated group, amoxicillin and clarithromycin-treated group and the positive control group. Conclusion: Antibiotics used for the eradication of H. pylori can also directly induce apoptosis in mouse B cell lymphoma cells, an action which involves the TNF system.",
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AU - Ishii, Hiromasa

AU - Hibi, Toshifumi

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N2 - Background: The effects of bacterial eradication therapy cannot be fully explained simply by elimination of the target bacteria, if one considers the effects of eradication therapy in H. pylori-negative cases of low-grade malignancy MALTomas of the rectum. The present study was undertaken to examine the possibility and mechanism of direct induction of apoptosis of the tumor cells by the antibiotics used for bacterial eradication therapy. Materials and Methods: A B cell lymphoma cell line (300-19) derived from BALB/c mice was co-cultured with amoxicillin or clarithromycin, and amoxicillin and clarithromycin at concentrations equal to or 1/10 × MIC of either drug. Cells cocultured with 1/100 × MIC of the standard anti-tumor agents, adriamycin, vincristine and cyclophosphamide, served as positive controls. Cells cultured without any antibiotic or anti-tumor agent served as controls. In each group, the following analyses were performed: (i) the time-course of changes in the cellular morphology, (ii) the time-course of occurrence of DNA fragmentation, (iii) the appearance of apoptotic changes as evaluated by trypan blue staining, (iv) Bcl-2 expression as examined by immunoblotting, and (v) the expression of TNFR1, Fas, FasL and caspase-3, -8 and -9, as evaluated by immunoblotting. Results: Cells treated with amoxicillin and clarithromycin showed the formation of apoptotic bodies, and degeneration and detachment of the cells in a dose-dependent manner. DNA fragmentation was induced in these cells to a degree similar to that seen in cells treated with the anti-tumor agents. Trypan blue staining also demonstrated apoptosis of the cells and loss of cell viability. Bcl-2 expression was seen only in the control group and FasL was never seen, while the expression of TNFR1, Fas and caspase-3, -8 and -9 was seen in the amoxicillin-treated group, clarithromycin-treated group, amoxicillin and clarithromycin-treated group and the positive control group. Conclusion: Antibiotics used for the eradication of H. pylori can also directly induce apoptosis in mouse B cell lymphoma cells, an action which involves the TNF system.

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