Scutellaria barbata D. Don induces G1/S arrest via modulation of p53             and Akt pathways in human colon carcinoma cells.
Cancer cells are characterized by an uncontrolled increase in cell proliferation.             G1 to S transition is one of the two main checkpoints used by cells to control             the cell cycle progress and cell proliferation. G1/S progression is highly regulated             by multiple intracellular signaling transduction cascades including Akt and p53             pathways, which therefore becomes a promising target for the development of novel             anticancer therapy. Scutellaria barbata D. Don (SB) is a major component in many             Chinese medicine formulas that have long been used in China to clinically treat             various cancers including colorectal cancer (CRC). Recently, we reported that             the ethanol extract of SB (EESB) is able to induce cancer cell apoptosis via activation             of the mitochondrion-dependent pathway and inhibit tumor angiogenesis through             suppression of Hedgehog signaling. To further elucidate the precise mechanisms             of its antitumor activity, in the present study we evaluated the effect of EESB             on the proliferation of human colon carcinoma HT-29 cells and investigated the             underlying molecular mechanism. We found that EESB could inhibit the proliferation             of HT-29 cells through blocking the G1/S cell cycle progression. In addition,             EESB treatment profoundly promoted antiproliferative p21 expression, but inhibited             the expression of pro-proliferative PCNA, cyclin D1 and CDK4 in HT-29 cells. Moreover,             the phosphorylation/activation of Akt was significantly suppressed by EESB treatment,             whereas that of p53 was enhanced. These results suggest that EESB could effectively             induce G1/S arrest in human colon carcinoma cells via modulation of multiple cell             cycle-related signaling pathways.
Academy of Integrative Medicine, Department of Pharmacology, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, PR China.
Lihui
L
Wei
Jiumao
J
Lin
Guangwen
G
Wu
Wei
W
Xu
Huang
H
Li
Zhenfeng
Z
Hong
Jun
J
Peng
D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D051058:Oncogene Protein v-akt / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D031363:Scutellaria; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D010936:Plant Extracts; C524947:Scutellaria barbata extract; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051058:Oncogene Protein v-akt