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The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells

  • Authors:
    • Yinzhi Lin
    • Kulrawee Sidthipong
    • Jun Ma
    • Naoki Koide
    • Kazuo Umezawa
    • Tetsuo Kubota
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi 480‑1195, Japan, Department of Research and Development, Shenzhen Wanhe Pharmaceutical Co., Ltd., Shenzhen, Guangdong 518107, P.R. China, Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480‑1195, Japan, Department of Microbiology and Immunology, Tokyo Medical and Dental University Graduate School of Health Care Sciences, Tokyo 113‑8510, Japan
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1092
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    Published online on: August 2, 2021
       https://doi.org/10.3892/etm.2021.10526
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Abstract

Plasmacytoma is one of the most difficult types of leukemia to treat, and it often invades the bone down to the marrow resulting in the development of multiple myeloma. NF‑κB is often constitutively activated, and promotes metastasis and drug resistance in neoplastic cells. The present study assessed the cellular anticancer activity of an NF‑κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on mouse plasmacytoma SP2/0 cells. Cellular invasion was measured by Matrigel chamber assay, and apoptosis was assessed by detecting caspase‑3 cleavage and by flow cytometric analysis with Annexin V. DHMEQ inhibited constitutively activated NF‑κB at nontoxic concentrations. DHMEQ was also shown to inhibit cellular invasion of SP2/0 cells, as well as human myeloma KMS‑11 and RPMI‑8226 cells. The metastasis PCR array indicated that DHMEQ induced a decrease in KISS1 receptor (KISS1R) expression in SP2/0 cells. Knockdown of KISS1R by small interfering RNA suppressed cellular invasion, suggesting that KISS1R may serve an essential role in the invasion of SP2/0 cells. Furthermore, DHMEQ enhanced cytotoxicity of the anticancer agent melphalan in SP2/0 cells. Notably, DHMEQ inhibited the expression of NF‑κB‑dependent anti‑apoptotic proteins, such as Bcl‑XL, FLIP, and Bfl‑1. In conclusion, inhibition of constitutively activated NF‑κB by DHMEQ may be useful for future anti‑metastatic and anticancer strategies for the treatment of plasmacytoma.
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Copy and paste a formatted citation
Spandidos Publications style
Lin Y, Sidthipong K, Ma J, Koide N, Umezawa K and Kubota T: The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells. Exp Ther Med 22: 1092, 2021.
APA
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., & Kubota, T. (2021). The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells. Experimental and Therapeutic Medicine, 22, 1092. https://doi.org/10.3892/etm.2021.10526
MLA
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., Kubota, T."The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells". Experimental and Therapeutic Medicine 22.4 (2021): 1092.
Chicago
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., Kubota, T."The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1092. https://doi.org/10.3892/etm.2021.10526
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Y, Sidthipong K, Ma J, Koide N, Umezawa K and Kubota T: The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells. Exp Ther Med 22: 1092, 2021.
APA
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., & Kubota, T. (2021). The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells. Experimental and Therapeutic Medicine, 22, 1092. https://doi.org/10.3892/etm.2021.10526
MLA
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., Kubota, T."The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells". Experimental and Therapeutic Medicine 22.4 (2021): 1092.
Chicago
Lin, Y., Sidthipong, K., Ma, J., Koide, N., Umezawa, K., Kubota, T."The designed NF‑κB inhibitor, DHMEQ, inhibits KISS1R‑mediated invasion and increases drug‑sensitivity in mouse plasmacytoma SP2/0 cells". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1092. https://doi.org/10.3892/etm.2021.10526
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