PMID- 32341329
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Apr 28
TI  - Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) 
      Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) 
      Pathway.
PG  - e922518
LID - 10.12659/MSM.922518 [doi]
AB  - BACKGROUND Thyroid cancer, which is the most common endocrine cancer, has shown a 
      drastic increase in incidence globally over the past decade. The present study 
      investigated the thyroid cancer-inhibitory potential of 
      jatrorrhizine-platinum(II) complex (JR-P(II) in vitro and in vivo. MATERIAL AND 
      METHODS The JR-P(II)-mediated cytotoxicity in thyroid carcinoma cells was 
      determined by using MTT assay. Assessment of acetylated histones, tubulin, and 
      DNA repair proteins was made by Western blot assays. Flow cytometry was used for 
      apoptosis and ROS accumulation measurement. RESULTS The JR-P(II) suppressed 
      proliferative capacity of SW1736, BHP7-13, and 8305C cells. JR-P(II) treatment 
      markedly promoted expression of acetylated histone H3, H4, and tubulin in a 
      dose-dependent manner. Treatment with JR-P(II) significantly elevated the 
      proportion of cells in sub-G1 and promoted cleaved caspase-3 and -9. In 
      JR-P(II)-treated cells, DCFH-DA fluorescence was much higher relative to control 
      cells. The JR-P(II) treatment consistently suppressed expression of pS6, 
      p-ERK1/2, p-4E-BP1, and p-AKT, and increased p-H2AX expression and suppressed 
      KU70 and KU80 protein levels. The level of RAD51 was repressed in 
      JR-P(II)-treated cells. JR-P(II) administration in mice caused no significant 
      change in body weight, and it inhibited SW1736 tumor growth in mice. CONCLUSIONS 
      The JR-P(II) induced cytotoxicity in thyroid cancer cells by inhibiting the 
      mechanism responsible for repair of double-stranded DNA. The in vivo data also 
      revealed that JR-P(II) effectively inhibits thyroid tumor growth by inducing DNA 
      damage. Thus, our results suggest that further evaluation of JR-P(II) as a 
      therapeutic candidate for thyroid cancer is warranted.
FAU - Lu, KeBin
AU  - Lu K
AD  - Department of General Surgery, Yuyao People's Hospital of Zhejiang Province, 
      Yuyao, Zhejiang, CA, China (mainland).
FAU - Wei, Wenjun
AU  - Wei W
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
FAU - Hu, Jiaqian
AU  - Hu J
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
FAU - Wen, Duo
AU  - Wen D
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
FAU - Ma, Ben
AU  - Ma B
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
FAU - Liu, Wanlin
AU  - Liu W
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Medical College, Fudan University, Shanghai, China 
      (mainland).
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
FAU - Lu, Zhongwu
AU  - Lu Z
AD  - Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 
      Shanghai, China (mainland).
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200428
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 091S1F8V5Q (jatrorrhizine)
RN  - 0I8Y3P32UF (Berberine)
RN  - 49DFR088MY (Platinum)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/drug effects
MH  - Berberine/*analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - China
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Platinum/metabolism/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Thyroid Gland/pathology
MH  - Thyroid Neoplasms/drug therapy/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC7201896
EDAT- 2020/04/29 06:00
MHDA- 2021/01/05 06:00
PMCR- 2020/04/28
CRDT- 2020/04/29 06:00
PHST- 2020/04/29 06:00 [entrez]
PHST- 2020/04/29 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/04/28 00:00 [pmc-release]
AID - 922518 [pii]
AID - 10.12659/MSM.922518 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Apr 28;26:e922518. doi: 10.12659/MSM.922518.