PMID- 31631173
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Oct 21
TI  - Antiproliferative Activity of Carnosic Acid is Mediated via Inhibition of Cell 
      Migration and Invasion, and Suppression of Phosphatidylinositol 3-Kinases 
      (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Signaling Pathway.
PG  - 7864-7871
LID - 10.12659/MSM.917735 [doi]
AB  - BACKGROUND Lung cancer is one of the leading causes of cancer-related mortalities 
      worldwide and majority of these deaths result from non-small cell lung cancer 
      (NSCLC). The primary objective of this research was to determine the anticancer 
      potential of carnosic acid, a plant derived abietane diterpene, against human 
      lung cancer cells, as well as to determine its effects on cell migration and 
      invasion, apoptosis, and the PI3K/AKT/m-TOR signaling pathway. MATERIAL AND 
      METHODS Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay; 
      fluorescence microscopy using acridine orange/ethidium bromide stain and Comet 
      assay were used to study cellular apoptosis. In vitro wound healing assay was 
      used to study effects on cell migration; Transwell assay was used to study cell 
      invasion after drug treatment. Western blot assay was used to study effects of 
      carnosic acid on the PI3K/AKT/m-TOR signaling pathway. RESULTS It was shown that 
      carnosic acid could inhibit the growth of A-549 human non-small cell lung 
      carcinoma cells dose-dependently showing an IC(5)(0) value of 12.5 muM. This growth 
      inhibition of A-549 cells was mediated via apoptotic cell death as observed by 
      fluorescence microscopy showing nuclear fragmentation and chromatin condensation. 
      Carnosic acid, dose-dependently, also inhibited cell migration and invasion. 
      Finally, western blot assay revealed that carnosic acid also led to inhibition of 
      the PI3K/AKT/m-TOR signaling pathway. CONCLUSIONS In conclusion, our results 
      showed that Carnosic acid has the potential to inhibit cancer cell growth in 
      A-549 lung cancer cells by activating apoptotic death, inhibiting cell migration 
      and invasion and suppressing PI3K/AKT/m-TOR signaling pathway.
FAU - Zhao, Liqun
AU  - Zhao L
AD  - Department of Respiratory Medicine, Xi'an No. 4 Hospital, Xi'an, Shaanxi, China 
      (mainland).
FAU - Zhang, Juanni
AU  - Zhang J
AD  - Prophylactic Medicine, School of Public Health, Xi'an Medical University, Xi'an, 
      Shaanxi, China (mainland).
FAU - Fan, Yinke
AU  - Fan Y
AD  - Pharmacology of Chinese Materia Medica, Institute of Traditional Chinese 
      Medicine, Shaanxi Academy of Traditional Chinese Medicine, Xi'an, Shaanxi, China 
      (mainland).
FAU - Li, Ya
AU  - Li Y
AD  - Department of Internal Medicine, Shaanxi Provincial Cancer Hospital, Xi'an, 
      Shaanxi, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20191021
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Abietanes)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - LI791SXT24 (salvin)
SB  - IM
MH  - A549 Cells
MH  - Abietanes/metabolism/*pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - China
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Neoplasm Invasiveness/physiopathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC6820331
COIS- Conflict of interest None.
EDAT- 2019/10/22 06:00
MHDA- 2020/02/19 06:00
PMCR- 2019/10/21
CRDT- 2019/10/22 06:00
PHST- 2019/10/22 06:00 [entrez]
PHST- 2019/10/22 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2019/10/21 00:00 [pmc-release]
AID - 917735 [pii]
AID - 10.12659/MSM.917735 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Oct 21;25:7864-7871. doi: 10.12659/MSM.917735.