Pyrrolidinedithiocarbamic Acid Ammonium Salt Inhibits Apoptosis and Phenotypic Transformation of Co-Culture of Myeloma Cells and Renal Tubular Epithelial Cells by Reducing the Secretion of Light Chain Protein
Background: We investigate the effects of NFκB inhibitor pyrrolidinedithiocarbamic acid ammonium salt (PDTC) on the viability, apoptosis and cell phenotype of HK-2 cells in the co-culture system of myeloma cells in renal tubular epithelial cells.
Methods: This study was performed in Qiqihar Medical University, Qiqihar, China from Jun 2018 to Jan 2019. RPMI-8226 cells and HK-2 cells were inoculated in the co-culture chamber and cultured to establish the co-culture system. An immunoturbidimetric assay was performed to detect κ light chain and λ light chain in RPMI-8226 cells. The effect of PDTC on the secretion of κ light chain and λ light chain of RPMI-8226 cells was detected by immunoturbidimetry and the ratio was calculated.
Results: PDTC significantly increased the viability of HK-2 cells. PDTC reduced the apoptosis of renal tubular epithelial cells. After PDTC treatment, the expression of cell surface marker E-cadherin decreased, and the expression of α-SMA increased, which induced the renal interstitial fibrosis. The secretion of κ light chain and λ light chain of RPMI-8226 cells was significantly decreased after the addition of PDTC, but the ratio was not changed.
Conclusion: PDTC can inhibit the cell activity, promote apoptosis, and reduce the secretion of secretion of κ light chain and λ light chain through inhibiting the NF-κB pathway activation of myeloma cell RPMI-8226.
2. Bilyy R, Tomin A, Mahorivska I, et al (2011). Antibody-mediated sialidase activity in blood serum of patients with multiple myeloma. J MolRecognit, 24(4): 576-84.
3. Ying WZ, Sanders PW (2001). Mapping the binding domain of immunoglobulin light chains for Tamm-Horsfall protein. Am J Pathol, 158(5): 1859-66.
4. Zhao A, Kong F, Liu CJ, et al (2017). Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma. Int J Mol Sci, 18(3): 513.
5. Wang PX, Sanders PW (2007). Immunoglobulin light chains generate hydrogen peroxide. J Am Soc Nephrol, 18(4): 1239-45.
6. Li ZW, Chen H, Campbell RA, et al (2008). NF-kappaB in the pathogenesis and treatment of multiple myeloma. Curr Opin Hematol, 15(4): 391-9.
7. Hideshima T, Chauhan D, Richardson P, et al (2002). NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem, 277(19): 16639-47.
8. Kumar SK, Lee JH, Lahuerta JJ, et al (2012). Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia, 26(1): 149-57.
9. Rumpold H, Salvador C, Wolf AM, et al (2007). Knockdown of PgP resensitizes leukemic cells to proteasome inhibitors. Biochem Biophys Res Commun, 361(2): 549-54.
10. Adams J (2004). The development of proteasome inhibitors as anticancer drugs. Cancer Cell, 5(5): 417-21.
11. Annunziata CM, Davis RE, Demchenko Y, et al (2007). Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell, 12(2): 115-30.
12. Parker KM, Ma MH, Manyak S, et al (2002). Identification of polymorphisms of the IkappaBalpha gene associated with an increased risk of multiple myeloma. Cancer Genet Cytogenet, 137(1): 43-8.
13. Bahlis NJ, King AM, Kolonias D, et al (2007). CD28-mediated regulation of multiple myeloma cell proliferation and survival. Blood, 109(11): 5002-10.
14. Anto RJ, Mukhopadhyay A, Shishodia S, et al (2002). Cigarette smoke condensate activates nuclear transcription factor-kappaB through phosphorylation and degradation of IkappaB(alpha): correlation with induction of cyclooxygenase-2. Carcinogenesis, 23(9): 1511-8.
15. Hassan SB, Gali-Muhtasib H, Göransson H, et al (2010). Alpha terpineol: a potential anticancer agent which acts through suppressing NF-kappaB signalling. Anticancer Res, 30(6): 1911-9.
16. Rajkumar SV, Dimopoulos MA, Palumbo A, et al (2014). International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol, 15(12): e538-48.
17. Paul S, Li L, Kalaga R, et al (1995). Natural catalytic antibodies: peptide-hydrolyzing activities of Bence Jones proteins and VL fragment. J Biol Chem, 270(25): 15257-61.
18. Matsuura K, Sinohara H (1996). Catalytic cleavage of vasopressin by human Bence Jones proteins at the arginylglycinamide bond. Biol Chem, 377(9): 587-9.
19. Shuster AM, Gololobov GV, Kvashuk OA, et al (1992). DNA hydrolyzing autoantibodies. Science, 256(5057): 665-7.
20. Matsuura K, Sinohara H (1996). Catalytic cleavage of vasopressin by human Bence Jones proteins at the arginylglycinamide bond. Biol Chem, 377(9): 587-9.
21. Sanders PW, Herrera GA, Galla JH (1987). Human Bence Jones protein toxicity in rat proximal tubule epithelium in vivo. Kidney Int, 32(6): 851-61.
22. Siezenga MA, van der Geest RN, Mallat MJ, et al (2010). Urinary properdin excretion is associated with intrarenal complement activation and poor renal function. Nephrol Dial Transplant, 25(4): 1157-1161.
23. Liu Y (2011). Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol, 7(12): 684-96.
24. Grande MT, Sánchez-Laorden B, López-Blau C, et al (2016). Erratum: Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med, 22(2): 217.
25. Lovisa S, LeBleu VS, Tampe B, et al (2015). Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med, 21(9): 998-1009.
|Issue||Vol 49 No 11 (2020)|
|Myeloma nephropathy Renal tubular epithelial cells Light chain protein|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|