PMID- 31322140
OWN - NLM
STAT- MEDLINE
DCOM- 20200213
LR  - 20221222
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Jul 8
TI  - Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma 
      Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and 
      Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT 
      Signaling Pathway.
PG  - 5054-5061
LID - 10.12659/MSM.915387 [doi]
AB  - <strong>BACKGROUND</strong> This study aimed to examine the effects of the 
      sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of 
      MDA-T32 human papillary thyroid carcinoma cells in vitro and in mouse tumor 
      xenografts. <strong>MATERIAL AND METHODS</strong> Cell proliferation and 
      viability of MDA-T32 human papillary thyroid carcinoma cells were determined by 
      MTT assay, and cell migration was studied using a transwell assay. Fluorescence 
      microscopy using acridine orange (AO) and ethidium bromide (EB) staining 
      evaluated apoptosis. Transmission electron microscopy was used to study the 
      effects of parthenolide on autophagy, and Western blot examined the levels of 
      autophagy-associated proteins, including Bax, Bcl-2, and LC3-ll. Mice (n=10) were 
      injected with 5x10(6) MDA-T32 cells subcutaneously into the left flank, and 
      xenograft tumors were grown for six weeks. Control untreated mice (n=5) were 
      compared with treated mice (n=5) given parthenolide three times per week. 
      <strong>RESULTS</strong> Parthenolide resulted in a dose-dependent reduction in 
      viability and cell migration of MDA-T32 cells, with a half-maximal inhibitory 
      concentration (IC(5)(0)) of 12 microM. AO and EB staining showed that parthenolide 
      induced cell apoptosis and electron microscopy identified autophagosomes in 
      MDA-T32 cells. Parthenolide induced increased expression of the autophagocytic 
      proteins, LC3-II and beclin-1, had a dose-dependent inhibitory effect on the 
      mTOR/PI3K/AKT cascade in MDA-T32 cells and inhibited the growth of the mouse 
      xenograft tumors in vivo. <strong>CONCLUSIONS</strong> Parthenolide inhibited the 
      growth and migration of MDA-T32 human papillary thyroid carcinoma cells in vitro 
      and mouse tumor xenografts and activated autophagy and apoptosis by 
      downregulation of the mTOR/PI3K/AKT signaling pathway.
FAU - Li, Chao
AU  - Li C
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Zhou, Yuqiu
AU  - Zhou Y
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Cai, Yongcong
AU  - Cai Y
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Shui, Chunyan
AU  - Shui C
AD  - Department of Otolaryngology - Head and Neck Surgery, The Affiliated Hospital of 
      Southwest Medical University, Luzhou, Sichuan, China (mainland).
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Otolaryngology - Head and Neck Surgery, The Affiliated Hospital of 
      Southwest Medical University, Luzhou, Sichuan, China (mainland).
FAU - Wang, Xu
AU  - Wang X
AD  - Graduate School, Chengdu Medical College, Chengdu, Sichuan, China (mainland).
FAU - Jiang, Jian
AU  - Jiang J
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Zeng, Dingfen
AU  - Zeng D
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Gui, Chunhan
AU  - Gui C
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
FAU - Sun, Ronghao
AU  - Sun R
AD  - Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, 
      Sichuan, China (mainland).
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20190708
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Sesquiterpenes)
RN  - 2RDB26I5ZB (parthenolide)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
RIN - Med Sci Monit. 2021 Mar 11;27:e931025. PMID: 33704264
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - China
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sesquiterpenes/metabolism/*pharmacology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Thyroid Cancer, Papillary/drug therapy/*metabolism
MH  - Thyroid Neoplasms/drug therapy/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC6637819
COIS- Conflict of interest None.
EDAT- 2019/07/20 06:00
MHDA- 2020/02/14 06:00
PMCR- 2019/07/08
CRDT- 2019/07/20 06:00
PHST- 2019/07/20 06:00 [entrez]
PHST- 2019/07/20 06:00 [pubmed]
PHST- 2020/02/14 06:00 [medline]
PHST- 2019/07/08 00:00 [pmc-release]
AID - 915387 [pii]
AID - 10.12659/MSM.915387 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Jul 8;25:5054-5061. doi: 10.12659/MSM.915387.