PMID- 35708264
OWN - NLM
STAT- MEDLINE
DCOM- 20220909
LR  - 20231213
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 36
IP  - 9
DP  - 2022 Sep
TI  - Ursolic acid inhibits the activation of smoothened-independent non-canonical 
      hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade.
PG  - 3555-3570
LID - 10.1002/ptr.7523 [doi]
AB  - It is being brought to light that smoothened (SMO)-independent non-canonical 
      Hedgehog signaling is associated with the pathogenesis of various cancers. 
      Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, 
      manifests potent effectiveness against multiple malignancies including colorectal 
      cancer (CRC). In our previous study, UA was found to protect against CRC in vitro 
      by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA 
      on SMO-independent non-canonical Hedgehog signaling in CRC was investigated in 
      the present study, which demonstrated that UA hampered the proliferation and 
      migration, induced the apoptosis of HCT-116(hSMO-) cells with SMO gene knockdown, 
      accompanied by the augmented expression of the suppressor of fused (SUFU), and 
      lessened levels of MYC (c-Myc), glioma-associated oncogene (GLI1) and Sonic 
      Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), 
      suggesting that UA diminished non-canonical Hedgehog signal transduction in CRC. 
      In HCT-116(hSMO-) xenograft tumor, UA ameliorated the symptoms, impeded the 
      growth and caused the apoptosis of CRC, with heightened SUFU expression, and 
      abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, 
      indicating that UA down-regulated non-canonical Hedgehog signaling cascade in 
      CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling-dependent 
      activation of SMO-independent non-canonical Hedgehog pathway.
CI  - (c) 2022 John Wiley & Sons Ltd.
FAU - Chen, Li
AU  - Chen L
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Liu, Maolun
AU  - Liu M
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Yang, Han
AU  - Yang H
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Ren, Shan
AU  - Ren S
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Sun, Qiang
AU  - Sun Q
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Zhao, Hui
AU  - Zhao H
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Ming, Tianqi
AU  - Ming T
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Tang, Shun
AU  - Tang S
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Tao, Qiu
AU  - Tao Q
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Zeng, Sha
AU  - Zeng S
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
FAU - Meng, Xianli
AU  - Meng X
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative 
      Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional 
      Chinese Medicine, Chengdu, China.
FAU - Xu, Haibo
AU  - Xu H
AUID- ORCID: 0000-0002-3713-3144
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, Department of 
      Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
LA  - eng
GR  - GJJJ2021003/Chengdu University of Traditional Chinese Medicine/
GR  - 2021MS447/Sichuan Provincial Administration of Traditional Chinese Medicine of 
      China/
GR  - 2021XYCZ007/Sichuan Provincial Administration of Traditional Chinese Medicine of 
      China/
GR  - 21PJ107/Health Commission of Sichuan Province of China/
GR  - 81173598/National Natural Science Foundation of China/
GR  - 81573813/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220616
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Triterpenes)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - *Colorectal Neoplasms/drug therapy
MH  - Hedgehog Proteins/metabolism
MH  - Humans
MH  - Oleanolic Acid/analogs & derivatives
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - *Triterpenes/pharmacology
MH  - Zinc Finger Protein GLI1/genetics
MH  - Ursolic Acid
OTO - NOTNLM
OT  - AKT
OT  - GLI1
OT  - colorectal cancer
OT  - non-canonical hedgehog signaling pathway
OT  - ursolic acid
EDAT- 2022/06/17 06:00
MHDA- 2022/09/11 06:00
CRDT- 2022/06/16 08:22
PHST- 2022/04/19 00:00 [revised]
PHST- 2021/12/13 00:00 [received]
PHST- 2022/04/23 00:00 [accepted]
PHST- 2022/06/17 06:00 [pubmed]
PHST- 2022/09/11 06:00 [medline]
PHST- 2022/06/16 08:22 [entrez]
AID - 10.1002/ptr.7523 [doi]
PST - ppublish
SO  - Phytother Res. 2022 Sep;36(9):3555-3570. doi: 10.1002/ptr.7523. Epub 2022 Jun 16.