FCY-302, a Novel Small Molecule, Induces Apoptosis in Leukemia and Myeloma Cells by Attenuating Key Antioxidant and Mitochondrial Enzymes

Abstract

Arylidene analogs are well proven for biological activities. FCY-302, a novel small molecule belonging to this class, was screened for its biological efficacy in leukemia and myeloma cells. FCY-302 selectively inhibited proliferation of cancer cells with GI50 values of 395.2 nM, 514.6 Nm, and 642.4 nM in HL-60, Jurkat, and RPMI-8226 cells, respectively. The compound also increased sub-G0 peak in the cancer cell cycle and favored apoptosis determined by annexin V assay. The compound decreased the antiapoptotic Bcl-2 levels and increased proapoptotic Bax proteins in leukemia and myeloma cell lines. FCY-302 attenuated the mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase enzyme activities and significantly decreased activities of antioxidant enzymes like SOD, CAT, GR, and GST in all the three cancer cells tested. Our findings suggest that FCY-302 inhibits the proliferation of leukemia and myeloma cancer cells by altering key mitochondrial and antioxidant enzymes, eventually driving them to apoptosis. These results drive focus on FCY-302 and its analogs to be developed as potential small molecules with bioactivities against cancer.

Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt

“…There was an accumulation in the sub-G 0 and G 2 /M phases of the cell cycle with FPMXY-14 treatments. The characteristic appearance of the sub-G 0 populations in a cell cycle indicates a loss of DNA content within the cells [13]. Our data, therefore, agreed with the reported literature and was also in line with the nuclear staining data, which indicated a condensed/fragmented nucleus of the Caki-1 and A-498 cells with FPMXY-14 treatments.…”

“…Cell proliferation was analyzed and performed as described elsewhere [13] with some modification. Normal or cancer cells were seeded in a 96-well plate at 5000 cells/well in a respective growth medium.…”

“…A signal at 194.86 δ in the 13 C NMR spectrum (Fig. 2 and Table 2) indicates the presence of α,β-unsaturated carbonyl carbon.…”

Cassia auriculata leaf extract ameliorates diabetic nephropathy by attenuating autophagic necroptosis via RIP‐1/RIP‐3‐p‐p38MAPK signaling

“…Cell viability was performed as described previously (Rajagopalan et al., 2019), with minor modifications. RGE cells grown in regular growth medium were seeded in a 96‐well plate (5,000 cells/well) and grown until they reached 80% confluency.…”

“…For in vivo analysis, kidney cells were lysed in RIPA buffer containing 50 mM Tris, 150 mM NaCl, 0.5% deoxycholate, 0.1% SDS, 2 mM EDTA, 0.1% Triton X‐100, 10% glycerol, 1 mM phenyl methyl sulfonyl fluoride, 10 μg/ml aprotinin and 5 μg/ml pepstatin A. Insoluble material was removed by centrifugation at 14,000 × g for 10 min at 4℃. Western blotting was performed as described previously (Rajagopalan et al., 2019), with few modifications. Total protein was quantified using a Coomassie plus protein assay reagent kit (Pierce; Rockford, IL, USA) and 20–40 μg protein was separated using SDS‐PAGE before being transferred to a nitrocellulose membrane that was probed with primary antibodies, and then incubated with HRP–conjugated secondary antibodies for 30 min.…”