The designed NF-κB inhibitor, DHMEQ, inhibits KISS1R-mediated invasion and increases drug-sensitivity in mouse plasmacytoma SP2/0 cells
| Autor: | Yinzhi Lin, Kazuo Umezawa, Kulrawee Sidthipong, Naoki Koide, Jun Ma, Tetsuo Kubota |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Small interfering RNA Matrigel DHMEQ Oncogene Chemistry Cell General Medicine Articles medicine.disease NF-κB melphalan multiple myeloma medicine.anatomical_structure Immunology and Microbiology (miscellaneous) plasmacytoma Apoptosis Annexin KISS1R Cancer research medicine Plasmacytoma Cytotoxicity |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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