2. Academic Validation
  3. Loss of Malignancy of Super-Methotrexate-resistant Osteosarcoma Cells Is Associated With an Increase of Methylated Histone Marks H3K9me3 and H3K27me3

Loss of Malignancy of Super-Methotrexate-resistant Osteosarcoma Cells Is Associated With an Increase of Methylated Histone Marks H3K9me3 and H3K27me3

  • Anticancer Res. 2024 Oct;44(10):4213-4218. doi: 10.21873/anticanres.17251.
Yusuke Aoki 1 2 3,  Yutaro Kubota 4 2,  Noriyuki Masaki 4 2,  Koya Obara 4 2,  Yasunori Tome 5,  Michael Bouvet 2,  Kotaro Nishida 3,  Robert M Hoffman 6 2
Affiliations

Affiliations

  • 1 AntiCancer Inc., San Diego, CA, U.S.A.; yaoki0630@gmail.com.
  • 2 Department of Surgery, University of California, San Diego, La Jolla, CA, U.S.A.
  • 3 Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
  • 4 AntiCancer Inc., San Diego, CA, U.S.A.
  • 5 Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan yastome@med.u-ryukyu.ac.jp.
  • 6 AntiCancer Inc., San Diego, CA, U.S.A.; all@anticancer.com.
PMID: 39348992 DOI: 10.21873/anticanres.17251
Abstract

Background/aim: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTXSR) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells.

Materials and methods: Previously selected 143B-MTXSR cells which are 5,500 times more MTX resistant than parental cells, were used for this study. The status of methylated histone H3K9me3 and H3K27me3 marks was examined with western immunoblotting and compared between 143B-MTXSR and parental 143B-P cells.

Results: Histone H3K9me3 and H3K27me3 marks were over-expressed in 143B-MTXSR compared to 143B-P (p<0.05, p<0.01, respectively).

Conclusion: Over-expression of histone H3K9me3 and H3K27me3 marks may be related to super-MTX resistance and to the loss of malignancy of super MTX-resistant osteosarcoma cells due to the fundamental relationship of methylation and Cancer.

Keywords

H3K27me3; H3K9me3; Osteosarcoma; histone; malignancy; methotrexate; methylation; resistance.

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