title: Hedyotis diffusaWilld. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells.
abstract: Recent studies have indicated that the inflammatory microenvironment plays a significant role in colorectal cancer (CRC). The interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway mediates the proliferative and anti-apoptotic activities required for oncogenesis under inflammatory conditions; thus, suppressing tumor growth by targeting the IL-6/STAT3 pathway is a promising therapeutic strategy for CRC. Our previous study reported that the ethanol extract obtained fromHedyotis diffusaWilld. (EEHDW) can induce apoptosis, and inhibit the proliferation of colon cancer cells and tumor angiogenesis by modulating various signaling pathways; however, less is known regarding the activity of EEHDW in a cancer-promoting inflammatory environment. Therefore, the present study investigated whether EEHDW inhibits the growth of the CRC HT-29 cell line via the IL-6/STAT3 signaling pathway. Pretreatment of HT-29 cells with IL-6 led to an increase in cell viability, colony formation and phosphorylated STAT3 (p-STAT3) expression. Treatment of these cells with EEHDW prior to IL-6 stimulation resulted in a significant reduction in the IL-6-induced phosphorylation of STAT3. In addition, EEHDW treatment significantly reduced the mRNA expression levels of cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma-2 (Bcl-2), and upregulated the expression levels of Bcl-2-associated X protein (P<0.05), which are important target genes of the IL-6/STAT3 pathway. These findings strongly indicated that EEHDW suppresses tumor cell growth and induces the apoptosis of human CRC cells via inactivation of the IL-6/STAT3 signaling pathway.
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Jiumao
authors: J
authors: Lin
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Qiongyu
authors: Q
authors: Li
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Hongwei
authors: H
authors: Chen
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Hui
authors: H
authors: Lin
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Zijun
authors: Z
authors: Lai
authors: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors: Jun
authors: J
authors: Peng
keywords: Hedyotis diffusa Willd; apoptosis; colorectal cancer; interleukin-6/signal transducer and activator of transcription 3 signaling pathway; proliferation