Page 4 - G. Cell differentiation. division. and death

[G. Cell differentiation, division, and death-5]

Effect of berberine on the cell differentiation of acute

promyelocytic leukemia (APL)

Hyein Noh¹, Aram Lee¹, Jihyun Lim¹, Jong-seok Lim¹

¹Biological Science, Sookmyung Women's University, Seoul 04310, Republic of Korea

Acute promyelocytic leukemia (APL) is characterized by the abnormal accumulation and rapid proliferation of
atypical promyelocytes that have impaired differentiation. Differentiation therapy with all-trans retinoic acid (ATRA)
is commonly applied to treat APL patients, but the long-term therapy with ATRA easily induces drug resistance.

Berberine (BBR) is natural isoquinoline alkaloid that is known to have antitumor properties by affecting various

biological functions. In the present study, we demonstrate the anti-tumor effects of BBR in the human APL cell line
HL-60. BBR in combination with ATRA significantly increased protein levels of differentiation markers including PU.1.
BBR also significantly increased the population of CD11b-positive cells and it showed a synergistic effect in

combination with low concentration of ATRA. BBR increased phosphorylation of AMPK as HL-60 differentiation was
in progress. When compound C, an AMPK inhibitor, was combined with BBR, the differentiation induced by BBR

was significantly inhibited. BBR also induced differentiation of the ATRA-resistant HL-60 cell line. In conclusion, these
findings suggest that BBR-mediated differentiation of HL-60 is affected by AMPK activation and BBR is expected to

be a new therapeutic option for APL patients.