Root Bark of Morus Alba L. Induced p53-Independent Apoptosis in Human Colorectal Cancer Cells by Suppression of STAT3 Activity.

ABSTRACT

The root bark of Morus alba L. (MA) used in traditional oriental medicine exerts various bioactivities including anticancer effects. In this study, we investigated the molecular mechanism underlying the methylene chloride extract of MA (MEMA)-induced apoptosis in colorectal cancer (CRC) cells. We observed that MEMA decreased cell viability and colony formation in both HCT116 p53+/+ cells and HCT116 p53-/- cells. In addition, MEMA increased the sub-G1 phase DNA content, the annexin V-positive cell population, and the expression of apoptosis marker proteins in both cell lines, indicating that MEMA induced apoptosis regardless of the p53 status. Interestingly, the phosphorylation level, transcriptional activity, and target genes expression of signal transducer and activator of transcription 3 (STAT3) were commonly decreased by MEMA. The overexpression of constitutively active STAT3 in HCT116 cells reversed MEMA-induced apoptosis, demonstrating that MEMA-triggered apoptosis was mediated by the inactivation of STAT3. Taken together, we suggest that MEMA can be applied not only to p53 wild-type CRC in the early stages but also to p53-mutant advanced CRC with hyperactivated STAT3. Even though a wide range of studies are required to validate the anticancer effects of MEMA, we propose MEMA as a novel material for the treatment of CRC.