PMID- 35171398
OWN - NLM
STAT- MEDLINE
DCOM- 20220525
LR  - 20220525
IS  - 1861-0293 (Electronic)
IS  - 1340-3443 (Linking)
VI  - 76
IP  - 3
DP  - 2022 Jun
TI  - Saikosaponin B1 and Saikosaponin D inhibit tumor growth in medulloblastoma 
      allograft mice via inhibiting the Hedgehog signaling pathway.
PG  - 584-593
LID - 10.1007/s11418-022-01603-8 [doi]
AB  - Medulloblastoma (MB), accounting for nearly 10% of all childhood brain tumors, 
      are implicated with aberrant activation of the Hedgehog (Hh) signaling pathway. 
      Saikosaponin B1 (SSB1) and Saikosaponin D (SSD), two bioactive constituents of 
      Radix Bupleuri, are reported to have many biological activities including 
      anticancer activities. In our work, we evaluated the inhibition of SSB1 and SSD 
      on MB tumor growth in allograft mice and explored the underlying mechanisms. The 
      associated biological activity was investigated in Shh Light II cells, an 
      Hh-responsive fibroblast cell line, using the Dual-Glo((R)) Luciferase Assay 
      System. First, SSB1 (IC(50), 241.8 nM) and SSD (IC(50), 168.7 nM) inhibited 
      GLI-luciferase activity in Shh Light II cells stimulated with ShhN CM, as well as 
      Gli1 and Ptch1 mRNA expression. In addition, both compounds suppressed the Hh 
      signaling activity provoked by smoothened agonist (SAG) or excessive Smoothened 
      (SMO) expression. Meanwhile, SSB1 and SSD did not inhibit glioma-associated 
      oncogene homolog (GLI) luciferase activity activated by abnormal expression of 
      downstream molecules, suppressor of fuse (SUFU) knockdown or GLI2 overexpression. 
      Consequently, SSB1 (30 mg/kg, ip) and SSD (10 mg/kg, ip) displayed excellent in 
      vivo inhibitory activity in MB allografts, and the tumor growth inhibition ratios 
      were approximately 50% and 70%, respectively. Our findings, thus, identify SSB1 
      and SSD significantly inhibit tumor growth in MB models by inhibiting the 
      Hedgehog pathway through targeting SMO.
CI  - (c) 2022. The Author(s) under exclusive licence to The Japanese Society of 
      Pharmacognosy.
FAU - Luo, Jia
AU  - Luo J
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China.
FAU - Wang, Juan
AU  - Wang J
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China.
FAU - Huang, Wenjing
AU  - Huang W
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China.
FAU - Liu, Junqiu
AU  - Liu J
AD  - Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang 
      Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of 
      China.
FAU - Tan, Wenfu
AU  - Tan W
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China. wftan@fudan.edu.cn.
FAU - Xin, Hong
AU  - Xin H
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 
      201203, People's Republic of China. xinhong@fudan.edu.cn.
LA  - eng
GR  - 81573655/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220216
PL  - Japan
TA  - J Nat Med
JT  - Journal of natural medicines
JID - 101518405
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Saponins)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - UR635J3F00 (saikosaponin D)
SB  - IM
MH  - Allografts/metabolism/pathology
MH  - Animals
MH  - *Cerebellar Neoplasms/genetics/metabolism/pathology
MH  - Hedgehog Proteins/genetics/metabolism
MH  - *Medulloblastoma/drug therapy/genetics/metabolism
MH  - Mice
MH  - Oleanolic Acid/analogs & derivatives
MH  - Saponins
MH  - Signal Transduction
MH  - Zinc Finger Protein GLI1/genetics/metabolism
OTO - NOTNLM
OT  - Hedgehog signaling pathway
OT  - Medulloblastoma
OT  - Saikosaponin B1
OT  - Saikosaponin D
OT  - Smoothened
EDAT- 2022/02/17 06:00
MHDA- 2022/05/26 06:00
CRDT- 2022/02/16 12:17
PHST- 2021/10/21 00:00 [received]
PHST- 2022/01/11 00:00 [accepted]
PHST- 2022/02/17 06:00 [pubmed]
PHST- 2022/05/26 06:00 [medline]
PHST- 2022/02/16 12:17 [entrez]
AID - 10.1007/s11418-022-01603-8 [pii]
AID - 10.1007/s11418-022-01603-8 [doi]
PST - ppublish
SO  - J Nat Med. 2022 Jun;76(3):584-593. doi: 10.1007/s11418-022-01603-8. Epub 2022 Feb 
      16.