Page 60 - I. Chemical biology and drug discovery
P. 60
[I. Chemical biology and drug discovery-33]
The root bark of MA induces p53-independent apoptosis in
HCT116 human colorectal carcinoma cells
Hyun-Ji Park¹, Shin-Hyung Park¹˙*
¹Department of Pathology, College of Korean Medicine, Dongeui University, Busan 47227, Korea
The aim of the current study is to investigate the anticancer activities of the root bark of MA in HCT116 human
colorectal carcinoma cells. Methylene chloride extract of MA (MEMA) decreased the cell viability and colony
formation in p53-wildtype HCT116 cells (HCT116 WT) and p53-null HCT116 cells (HCT116 p53-/-). We next examined
whether the anticancer effects of MEMA are related with apoptosis induction. MEMA increased chromatin
condensation and up-regulated the expression of cleaved PARP and cleaved caspase-3. MEMA also enhanced the
sub-G1 DNA content and annexin V-positive cells. These phenomena were observed in both HCT116 WT and
HCT116 p53-/- cells, demonstrating that MEMA induced apoptosis by p53-independent mechanism. As a molecular
mechanism, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was commonly decreased
by MEMA in both cell lines. The nuclear translocation of STAT3 and the expression of STAT3 target genes were also
reduced by MEMA. Transfection of constitutively active STAT3 reversed the anti-proliferative effect of MEMA in
HCT116 cells. Taken together, our results demonstrate that MEMA induced p53-independent apoptosis in HCT116
cells by suppression of STAT3 (NRF-2019R1F1A1059588).
