Fig. 5.

Fisetin targets senescent cholangiocytes in vitro.

(A) Senolytic compounds at various concentrations were applied to proliferating and senescent cholangiocytes (induced experimentally by irradiation). Fisetin and A1331 significantly reduced the number of senescent cholangiocytes as measured by Crystal violet. Bars represent mean ± SEM; n = 4. (B,C) Fisetin and A1331 induced apoptosis in senescent cholangiocytes. (D) Fisetin did not induce apoptosis in non-proliferating or non-senescent cholangiocytes. Proliferating and senescent cholangiocytes were treated with fisetin and A1331, respectively for 12 h and Caspase-3/7 activity was measured using a luminescent substrate. (F) Fisetin did not induce apoptosis in isolated hepatocytes from WT or Mdr2^-/- mice. Data represent mean ± SD; n = 4 at each concentration. ∗p <0.01 (Student’s t test). Mdr2, multidrug-resistance 2; NHC, normal human cholangiocyte; WT, wild-type.