AI Article Synopsis
- The study examined the role of cystathionine β synthase (CBS) and hydrogen sulfide (H2S) signaling in multiple myeloma patients, finding elevated CBS levels in these patients compared to healthy controls.
- AOAA, a CBS inhibitor, significantly reduced U266 cell proliferation and altered cell cycle distribution, while the CSE inhibitor PAG had no effect; NaHS was shown to promote cell cycle progression and counteracted AOAA's effects.
- The research suggests that the CBS/H2S system influences both the growth and programmed cell death of multiple myeloma cells.
Article Abstract
Objective-To investigate cystathionine β synthase (CBS)/hydrogen sulfide (H2S) signaling in multiple myeloma (MM) patients and to identify its effect on the proliferation of U266 cells. Methods-Bone marrow samples of 19 MM patients and 23 healthy donors were collected. qRT-PCR was performed to measure the mRNA expression levels of H2S synthases, cystathionine β synthase, and cystathionine γ lyase. ELISA assays quantified the amount of H2S produced by the two enzymes CBS and CSE. CCK-8 experiment was used to investigate the influence of the CBS inhibitor amino oxyacetic acid and the CSE inhibitor propargylglycine on the proliferation of U266 cells. Flow cytometry and western blotting were performed to determine the effects of AOAA, PAG, and NaHS on cell cycle distribution as well as Caspase-3 and Bcl-2 expression. Results-Patients with MM had higher level of CBS compared with healthy donors. AOAA significantly inhibited cell proliferation in both a time and concentration dependent characteristic, whereas PAG does not. After 24 hours of treatment, AOAA significantly elevated the G0/G1 phase proportion of cells, and reduced the cell distribution in both S and G2/M phases, while NaHS accelerated cell cycle progression by reducing the relative number of cells in G0/G1 phase and increasing the proportion of cells in the G2/M phase. Moreover, AOAA abolished the impact of NaHS on cell cycle progression of U266 cells. AOAA treatment also led to a significant decrease in Bcl-2 expression and dramatic increase in Caspase-3 expression, though NaHS reversed these effects. Conclusion-CBS/H2S system might have a certain effect on the proliferation and apoptosis of MM cells.
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| http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2020034851 | DOI Listing |
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