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Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity. 2023

Hui Zhao, and Shun Tang, and Qiu Tao, and Tianqi Ming, and Jiarong Lei, and Yuanjing Liang, and Yuhui Peng, and Minmin Wang, and Maolun Liu, and Han Yang, and Shan Ren, and Haibo Xu
State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Overwhelming evidence points to an abnormally active Wnt/β-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/β-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/β-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/β-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/β-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000097245 Ursolic Acid A pentacyclic triterpene that co-occurs with its isomer OLEANOLIC ACID in several plant species, and occurs in large amounts in FRUITS (such as CRANBERRIES; PEARS; PLUMS; and OLIVES), MEDICINAL HERBS, and other plants. (+)-Ursolic Acid,(3 beta)-3-Hydroxyurs-12-en-28-oic Acid,3-Epi-Ursolic Acid,3-Epiursolic Acid,3alpha-Ursolic Acid,3beta-Ursolic Acid,Olean-12-en-28-oic Acid, 3-Hydroxy-, Sodium Salt (1:1), (3beta)-,Sodium Oleanolate,Ursolic Acid Monosodium Salt,Ursolic Acid Sodium Salt,Ursolic Acid, (3beta)-Isomer, 2-(14)C-Labeled,Ursolic Acid, (3beta)-Isomer, Monopotassium Salt,Merotaine,3 Epi Ursolic Acid,3 Epiursolic Acid,3alpha Ursolic Acid,3beta Ursolic Acid,Oleanolate, Sodium
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015179 Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. Colorectal Cancer,Colorectal Carcinoma,Colorectal Tumors,Neoplasms, Colorectal,Cancer, Colorectal,Cancers, Colorectal,Carcinoma, Colorectal,Carcinomas, Colorectal,Colorectal Cancers,Colorectal Carcinomas,Colorectal Neoplasm,Colorectal Tumor,Neoplasm, Colorectal,Tumor, Colorectal,Tumors, Colorectal
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D051176 beta Catenin A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS. beta-Catenin,Catenin, beta
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D060449 Wnt Signaling Pathway A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, and the vertebrate INT gene. The signaling pathway is initiated by the binding of WNT PROTEINS to cell surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN. Wnt Signaling,Wnt Pathway,Wnt Pathway, Canonical,Wnt beta-Catenin Signaling Pathway,Canonical Wnt Pathway,Canonical Wnt Pathways,Pathway, Canonical Wnt,Pathway, Wnt,Pathway, Wnt Signaling,Signaling Pathway, Wnt,Signaling, Wnt,Wnt Signaling Pathways,Wnt Signalings,Wnt beta Catenin Signaling Pathway

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