MOLM-14 (A, B) and MV4-11 (C) cells made
resistant to Venetoclax or drug-naïve were treated with the indicated
drug combinations (MOLM-14: CNL 15μM, Ara-C 1.25μM, venetoclax
50nM; MV4-11: CNL 15 μM, Ara-C 1.25 μM) for 24 hours, harvested
and proteins extracted. Western blots were performed and quantitated via
densitometry. Loading was normalized to actin (3A, 3B) or to tubulin (3C). Shown
is mean +/− S.E.M. of relative protein expression to vehicle for proteins
indicated, N=3–5. Of note, we chose tubulin instead of actin for the
MV4-11 drug-resistant cell line as actin levels were significantly reduced in
this cell lines compared with wild type (data not shown). Even though, CNL
elevated tubulin in wild type but not the drug-resistant cell line. CNL reduced
Mcl-1 and P-S317-Chk1 significantly in the drug-resistant cell line.
A: *, p<0.05 vs. vehicle; #, p<0.05 vs. triple.
B:*, p<0.005 vs. Ara-C; #, p<0.005 vs. triple.
C: *, p<0.05 vs. vehicle drug-naïve; ; ^, p=0.05
vs. vehicle drug-naive; #, P<0.02 vs. Ara-C drug-naive; <, p=0.048
vs. Ara-C drug-naive. Representative blots are shown beneath each graph.