@Article{biocell.2024.051074,
AUTHOR = {RUOYU CHEN, YIMAN WU, FENG WANG, JUNTAO ZHOU, HUAZHANG ZHUANG, WEI LI},
TITLE = {Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway},
JOURNAL = {BIOCELL},
VOLUME = {48},
YEAR = {2024},
NUMBER = {7},
PAGES = {1037--1046},
URL = {http://www.techscience.com/biocell/v48n7/57226},
ISSN = {1667-5746},
ABSTRACT = { <b>Background:</b> Oleanolic acid (OA), a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity, was isolated from traditional Chinese medicinal herbs. Conversely, the OA that impacts colon cancer (CC) cells and its underlying mechanisms remain poorly understood. <b>Methods:</b> The cytotoxic effect of OA alone or OA-5-Fluorouracil (5-FU) combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide (MTT). Then, the impact of OA on CC cell lines (LoVo and HT-29) proliferation and stemness were measured using colon formation and tumorsphere formation assays. Octamer-binding transcription factor 4 (Oct4), Prominin-1 (CD133), Nanog, and transcription factor SOX-2 (SOX2) are cell stemness-related indicators whose expression was assessed using fluorescence qPCR assay, Western blotting, and immunohistochemistry. The effect of OA on the proliferative potency of CC cells was evaluated using an <i>in vivo</i> model. <b>Results:</b> The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU. Moreover, OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers (CD133, Nanog, SOX2, and Oct4) expression levels both <i>in vitro</i> and <i>in vivo</i>, as well as by inactivating the activator of transcription 3 (STAT3 signaling) and Janus kinase 2/signal transducer (JAK2). <b>Conclusion:</b> These findings imply that oleanolic acid, both <i>in vitro</i> and <i>in vivo</i>, suppresses the JAK2/STAT3 pathway, which in turn reverses chemoresistance and decreases colon cancer cell stemness. Therefore, by reducing the recommended amount of 5-FU, this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.},
DOI = {10.32604/biocell.2024.051074}
}