PMID- 35293266
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220716
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 3
DP  - 2022 Mar
TI  - Shikonin induces apoptosis and autophagy via downregulation of 
      pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells.
PG  - 7904-7918
LID - 10.1080/21655979.2022.2052673 [doi]
AB  - Shikonin(SK) is a natural small molecule naphthoquinone compound, which has 
      anti-cancer activity in various human malignant tumors. Pyrroline-5-carboxylate 
      reductase 1(PYCR1) is involved in tumorigenesis and regulates various cellular 
      processes, including growth, invasion, migration, and apoptosis. However, the 
      effect of SK and PYCR1 on apoptosis and autophagy in hepatocellular carcinoma are 
      unclear. Our goal is to determine the internal molecular mechanism of the 
      interaction between SK and PYCR1 and its role in the occurrence and development 
      of liver cancer. The CCK8 assay, wound healing assay, and transwell assays show 
      that SK and siPYCR1(gene silence PYCR1) inhibited the malignant phenotype of HCC 
      cells, including cell viability, colony formation, migration, and invasion, 
      respectively. The flow cytometry assays and immunofluorescence show that SK and 
      siPYCR1 activated apoptosis and autophagy, respectively. SK induces apoptosis and 
      autophagy in a dose-dependent manner. In addition, HCC cells were transfected 
      with small interference fragment PYCR1 siRNA to construct siPYCR1 and SK single 
      treatment group and co-treatment group to verify the interaction between SK and 
      PYCR1. The Western blot identified that PI3K/Akt/mTOR signal pathway protein 
      expression was significantly downregulated in HCC cells treated with SK and 
      siPYCR1 together. Collectively, SK may induce apoptosis and autophagy by reducing 
      the expression of PYCR1 and suppressing PI3K/Akt/mTOR. Thus, SK may be a 
      promising antineoplastic drug in Hepatocellular carcinoma (HCC). SK 
      downregulating PYCR1 might supply a theoretical foundation for the potential 
      therapeutic application in hepatocellular carcinoma.
FAU - Zhang, Junli
AU  - Zhang J
AD  - Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory 
      Diagnosis, Bengbu Medical College, Bengbu, China.
FAU - Shang, Ling
AU  - Shang L
AD  - Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory 
      Diagnosis, Bengbu Medical College, Bengbu, China.
FAU - Jiang, Wendi
AU  - Jiang W
AD  - Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory 
      Diagnosis, Bengbu Medical College, Bengbu, China.
FAU - Wu, Wenjuan
AU  - Wu W
AD  - Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, 
      Bengbu Medical College, Bengbu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Naphthoquinones)
RN  - 0 (Pyrroles)
RN  - 2906-39-0 (delta-1-pyrroline-5-carboxylate)
RN  - 3IK6592UBW (shikonin)
RN  - EC 1.5.1.- (Pyrroline Carboxylate Reductases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis
MH  - Autophagy
MH  - *Carcinoma, Hepatocellular/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Down-Regulation
MH  - Humans
MH  - *Liver Neoplasms/metabolism
MH  - *Naphthoquinones/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrroles
MH  - Pyrroline Carboxylate Reductases/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC9208523
OTO - NOTNLM
OT  - PYCR1
OT  - Shikonin
OT  - apoptosis
OT  - autophagy
OT  - hepatocellular carcinoma
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/03/17 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/03/16
CRDT- 2022/03/16 08:43
PHST- 2022/03/16 08:43 [entrez]
PHST- 2022/03/17 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/03/16 00:00 [pmc-release]
AID - 2052673 [pii]
AID - 10.1080/21655979.2022.2052673 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Mar;13(3):7904-7918. doi: 10.1080/21655979.2022.2052673.