PMID- 36062172
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220907
IS  - 1741-427X (Print)
IS  - 1741-4288 (Electronic)
IS  - 1741-427X (Linking)
VI  - 2022
DP  - 2022
TI  - Ethyl Acetate Fraction of Hedyotis diffusa Willd Induces Apoptosis via JNK/Nur77 
      Pathway in Hepatocellular Carcinoma Cells.
PG  - 1932777
LID - 10.1155/2022/1932777 [doi]
LID - 1932777
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by poor diagnosis and 
      high mortality. Novel and efficient therapeutic agents are urgently needed for 
      the treatment. Hedyotis diffusa Willd (HDW) is used to treat cancers, especially 
      HCC in China. PURPOSE: The study aimed to identify the main anti-HCC extract in 
      HDW and to explore the mechanism of the active extract. MATERIALS AND METHODS: 
      The high-performance liquid chromatography-quadrupole-time of flight mass 
      spectrometry (HPLC-QTOF-MS) method was used for the simultaneous determination of 
      main compounds in the ethyl acetate fraction of HDW (EHDW). The toxicity test of 
      different HDW fractions was carried out on larvae at 2 day-post-fertilization 
      (dpf) for 72 h. The in vivo anti-HCC effect of different HDW fractions was 
      evaluated on a zebrafish tumor model by immersion administration. The 
      antiproliferative effect of HDW fractions was determined with MTT assay, as well 
      as hematoxylin and eosin (HE) staining assay. Hoechst 33258 staining was used to 
      observe changes in nucleus morphology. Flow cytometry analysis was used to 
      investigate apoptosis induction. Western blot analysis was used to examine 
      apoptosis-related proteins, and key proteins in JNK/Nur77 signaling pathway. 
      SP600125 was served to validate the apoptotic mechanism. RESULTS: EHDW showed the 
      strongest tumor cell growth inhibitory effect on zebrafish tumor model. Further 
      study revealed that EHDW induced apoptosis in zebrafish tumor model and in 
      cultured Hep3B cells. Meanwhile, it has been shown that the levels of 
      BCL2-associated X (Bax), cytochrome c (cyto c), cleaved-caspase 3, and 
      poly-ADP-ribose polymerase (PARP) cells were upregulated. In contrast, the level 
      of antiapoptotic B cell lymphoma-2 (Bcl-2) was downregulated in Hep3B cells. 
      Additionally, EHDW activated JNK/Nur77 pathway by increasing the levels of 
      p-JNK((Thr183/Tyr185)) and p-Nur77((Ser351)). Further study showed that blockage 
      of JNK by SP600125 reversed EHDW-induced JNK/Nur77 pathway and the downstream 
      apoptotic proteins. CONCLUSION: In conclusion, EHDW exerted the anti-HCC effect, 
      which may be attributed to the activation of JNK/Nur77 pathway. This study 
      supported the rationale of HDW as an HCC therapeutic agent.
CI  - Copyright (c) 2022 Weimin Ning et al.
FAU - Ning, Weimin
AU  - Ning W
AD  - Dongguan Hospital of Chinese Medicine affiliated to Guangzhou University of 
      Chinese Medicine, Dongguan 523005, China.
FAU - Xu, Nishan
AU  - Xu N
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Zhou, Chunhong
AU  - Zhou C
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Zou, Lifang
AU  - Zou L
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Quan, Jingyu
AU  - Quan J
AUID- ORCID: 0000-0002-2378-7366
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Yang, Hua
AU  - Yang H
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Lu, Zinbin
AU  - Lu Z
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Cao, Huihui
AU  - Cao H
AUID- ORCID: 0000-0001-5297-4702
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
FAU - Liu, Junshan
AU  - Liu J
AUID- ORCID: 0000-0003-3744-6180
AD  - Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory 
      of State Administration of Traditional Chinese Medicine, School of Traditional 
      Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
AD  - Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 
      510515, China.
LA  - eng
PT  - Journal Article
DEP - 20220824
PL  - United States
TA  - Evid Based Complement Alternat Med
JT  - Evidence-based complementary and alternative medicine : eCAM
JID - 101215021
PMC - PMC9433286
COIS- The authors claim no conflicts of interest.
EDAT- 2022/09/06 06:00
MHDA- 2022/09/06 06:01
PMCR- 2022/08/24
CRDT- 2022/09/05 04:21
PHST- 2021/11/15 00:00 [received]
PHST- 2022/04/22 00:00 [revised]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/09/05 04:21 [entrez]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/06 06:01 [medline]
PHST- 2022/08/24 00:00 [pmc-release]
AID - 10.1155/2022/1932777 [doi]
PST - epublish
SO  - Evid Based Complement Alternat Med. 2022 Aug 24;2022:1932777. doi: 
      10.1155/2022/1932777. eCollection 2022.