PMID- 29328421
OWN - NLM
STAT- MEDLINE
DCOM- 20180831
LR  - 20211204
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 39
IP  - 3
DP  - 2018 Mar
TI  - Antitumor activity of curcumin by modulation of apoptosis and autophagy in human 
      lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway.
PG  - 1523-1531
LID - 10.3892/or.2018.6188 [doi]
AB  - Curcumin is known to exhibit anticancer effects on various cancers with selective 
      cytotoxicity in tumor cells. In the present study, the effects of 
      curcumin‑induced multiple PCDs on human non‑small cell lung cancer (NSCLC) cells 
      and the potential molecular mechanisms of apoptosis and autophagy triggered by 
      curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed 
      by co‑culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor 
      LY294002. The anti‑proliferation effect of different stimulus was measured by MTT 
      assay. Apoptosis was detected by flow cytometry. Autophagy induction was detected 
      by MDC labeling and western blotting of Beclin1, LC3, and p62 expression. The 
      mRNA and protein expression levels of Akt and mTOR were assayed by real‑time 
      fluorescence quantitative (qRT‑PCR) technique and western blotting. Our results 
      showed that curcumin inhibited the viability of A549 cells time‑ and 
      dose‑dependently. In addition, a dosage-dependent A549 cell apoptosis‑induction 
      phenomena was observed by the curcumin intervention. Moreover, obvious autophagy 
      was induced after curcumin‑treatment, characterized by the formation of 
      fluorescent particles [autophagic vesicles (AVs)] and significant increase in 
      ratio of LC3‑Ⅱ/LC3‑Ⅰ and Beclin1 as well as decreased p62 expression. 
      Furthermore, the effect of curcumin on a substantial downregulation of 
      phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) 
      pathway was observed. It is worth noting that the inhibition of mTOR by rapamycin 
      or of PI3K/Akt by LY294002 augmented curcumin‑induced apoptosis and autophagy, 
      leading to significant inhibition of cell proliferation. From these findings, it 
      can be speculated that curcumin potently inhibit the cell growth of NSCLC A549 
      cells through inducing both apoptosis and autophagy by inhibition of the 
      PI3K/Akt/mTOR pathway. These results support the potential use of curcumin as a 
      novel candidate in treatment of human lung cancer.
FAU - Liu, Furong
AU  - Liu F
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Gao, Song
AU  - Gao S
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Yang, Yuxuan
AU  - Yang Y
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Zhao, Xiaodan
AU  - Zhao X
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Fan, Yameng
AU  - Fan Y
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Ma, Wenxia
AU  - Ma W
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Yang, Danrong
AU  - Yang D
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Yang, Aimin
AU  - Yang A
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi 710061, P.R. China.
FAU - Yu, Yan
AU  - Yu Y
AD  - School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 
      Shaanxi 710061, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180104
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - *Autophagy
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Proliferation/drug effects
MH  - Curcumin/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Lung Neoplasms/drug therapy/metabolism/*pathology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2018/01/13 06:00
MHDA- 2018/09/01 06:00
CRDT- 2018/01/13 06:00
PHST- 2017/08/04 00:00 [received]
PHST- 2017/12/29 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/09/01 06:00 [medline]
PHST- 2018/01/13 06:00 [entrez]
AID - 10.3892/or.2018.6188 [doi]
PST - ppublish
SO  - Oncol Rep. 2018 Mar;39(3):1523-1531. doi: 10.3892/or.2018.6188. Epub 2018 Jan 4.