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Extensive DNA Damage and Loss of Cell Viability Occur Synergistically With the Combination of Recombinant Methioninase and Paclitaxel on Pancreatic Cancer Cells which Report DNA-Damage Response in Real Time

SEI MORINAGA, QINGHONG HAN, KOHEI MIZUTA, BYUNG MO KANG, MOTOKAZU SATO, MICHAEL BOUVET, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, TAKASHI HIGUCHI, HIROYUKI TSUCHIYA, SATORU DEMURA and ROBERT M. HOFFMAN
Cancer Genomics & Proteomics November 2024, 21 (6) 585-590; DOI: https://doi.org/10.21873/cgp.20475
SEI MORINAGA
1AntiCancer Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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QINGHONG HAN
1AntiCancer Inc., San Diego, CA, U.S.A.
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KOHEI MIZUTA
1AntiCancer Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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BYUNG MO KANG
1AntiCancer Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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MOTOKAZU SATO
1AntiCancer Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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MICHAEL BOUVET
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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NORIO YAMAMOTO
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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KATSUHIRO HAYASHI
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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HIROAKI KIMURA
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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SHINJI MIWA
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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KENTARO IGARASHI
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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TAKASHI HIGUCHI
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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HIROYUKI TSUCHIYA
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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SATORU DEMURA
3Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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ROBERT M. HOFFMAN
1AntiCancer Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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  • For correspondence: all{at}anticancer.com
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    Figure 1.

    Paclitaxel and recombinant methioninase (rMETase) treatment of MiaPaCa-2Tet-On 53BP1-GFP cells. (A) Sensitivity of MiaPaCa-2Tet-On 53BP1-GFP cells to paclitaxel. (B) Sensitivity of MiaPaCa-2Tet-On 53BP1-GFP cells to rMETase (mean±standard deviation, n=3).

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    Figure 2.

    Efficacy of the combination of paclitaxel and rMETase on MiaPaCa-2Tet-On 53BP1-GFP cells. The combination of recombinant methioninase (rMETase) (1.66 U/ml [IC25]) and paclitaxel (3.31 nM [IC25]) was synergistic for MiaPaCa-2Tet-On 53BP1-GFP cells. n=3 *p<0.05 using Tukey-Kramer analysis.

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    Figure 3.

    Effect of paclitaxel alone, recombinant methioninase (rMETase) alone and their combination on DNA damage in MiaPaCa-2Tet-On 53BP1-GFP cells. Cells were untreated (Control) or treated with 5.1 nM (IC50) paclitaxel alone, 2.3 U/ml (IC50) rMETase alone or their combination. (A) Images of DNA damage and repair in MiaPaCa-2Tet-On 53BP1-GFP cells expressing green fluorescent protein (GFP). Scale bars: 100 μm. (B) Quantification of DNA damage in treated cells. GFP fluorescence was observed with an IX71 fluorescence microscope (Olympus, Tokyo, Japan). *p<0.05 (n=6) using Tukey-Kramer analysis.

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Cancer Genomics - Proteomics: 21 (6)
Cancer Genomics & Proteomics
Vol. 21, Issue 6
November-December 2024
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Extensive DNA Damage and Loss of Cell Viability Occur Synergistically With the Combination of Recombinant Methioninase and Paclitaxel on Pancreatic Cancer Cells which Report DNA-Damage Response in Real Time
SEI MORINAGA, QINGHONG HAN, KOHEI MIZUTA, BYUNG MO KANG, MOTOKAZU SATO, MICHAEL BOUVET, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, TAKASHI HIGUCHI, HIROYUKI TSUCHIYA, SATORU DEMURA, ROBERT M. HOFFMAN
Cancer Genomics & Proteomics Nov 2024, 21 (6) 585-590; DOI: 10.21873/cgp.20475

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Extensive DNA Damage and Loss of Cell Viability Occur Synergistically With the Combination of Recombinant Methioninase and Paclitaxel on Pancreatic Cancer Cells which Report DNA-Damage Response in Real Time
SEI MORINAGA, QINGHONG HAN, KOHEI MIZUTA, BYUNG MO KANG, MOTOKAZU SATO, MICHAEL BOUVET, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, TAKASHI HIGUCHI, HIROYUKI TSUCHIYA, SATORU DEMURA, ROBERT M. HOFFMAN
Cancer Genomics & Proteomics Nov 2024, 21 (6) 585-590; DOI: 10.21873/cgp.20475
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Keywords

  • DNA damage
  • synergy
  • rMETase
  • paclitaxel
  • methionine addiction
  • Hoffman effect
  • methionine restriction
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