PMID- 33530617
OWN - NLM
STAT- MEDLINE
DCOM- 20210906
LR  - 20211204
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 26
IP  - 3
DP  - 2021 Jan 26
TI  - Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of 
      AKT/mTOR and Epithelial-to-Mesenchymal Transition.
LID - 10.3390/molecules26030638 [doi]
LID - 638
AB  - Cancer metastasis is the major cause of about 90% of cancer deaths. As 
      epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, 
      this study aimed to elucidate the effect of ovalitenone on the suppression of EMT 
      and metastasis-related behaviors, including cell movement and growth under 
      detached conditions, and cancer stem cells (CSCs), of lung cancer cells. METHODS: 
      Cell viability and cell proliferation were determined by 
      3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony 
      formation assays. Cell migration and invasion were analyzed using a wound-healing 
      assay and Boyden chamber assay, respectively. Anchorage-independent cell growth 
      was determined. Cell protrusions (filopodia) were detected by 
      phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by 
      spheroid formation. The proteins involved in cell migration and EMT were 
      evaluated by Western blot analysis and immunofluorescence staining. RESULTS: 
      Ovalitenone was used at concentrations of 0-200 muM. While it caused no cytotoxic 
      effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed 
      anchorage-independent growth, CSC-like phenotypes, colony formation, and the 
      ability of the cancer to migrate and invade cells. The anti-migration activity 
      was confirmed by the reduction of filopodia in the cells treated with 
      ovalitenone. Interestingly, we found that ovalitenone could significantly 
      decrease the levels of N-cadherin, snail, and slug, while it increased 
      E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of 
      focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian 
      target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by 
      ovalitenone. CONCLUSIONS: The results suggest that ovalitenone suppresses EMT via 
      suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited 
      potential for the suppression of CSC phenotypes. These data reveal the 
      anti-metastasis potential of the compound and support the development of 
      ovalitenone treatment for lung cancer therapy.
FAU - Sanookpan, Kittipong
AU  - Sanookpan K
AD  - Cell-Based Drug and Health Product Development Research Unit, Faculty of 
      Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
AD  - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, 
      Chulalongkorn University, Bangkok 10330, Thailand.
FAU - Nonpanya, Nongyao
AU  - Nonpanya N
AD  - Cell-Based Drug and Health Product Development Research Unit, Faculty of 
      Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
AD  - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, 
      Chulalongkorn University, Bangkok 10330, Thailand.
FAU - Sritularak, Boonchoo
AU  - Sritularak B
AD  - Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical 
      Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
FAU - Chanvorachote, Pithi
AU  - Chanvorachote P
AD  - Cell-Based Drug and Health Product Development Research Unit, Faculty of 
      Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
AD  - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, 
      Chulalongkorn University, Bangkok 10330, Thailand.
LA  - eng
GR  - The 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot 
      Endowment Fund)/Chulalongkorn University/
GR  - RSA6180036/Thailand Research Fund/
PT  - Journal Article
DEP - 20210126
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Phytochemicals)
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  - A549 Cells
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lung Neoplasms/drug therapy/*metabolism
MH  - Millettia/*chemistry
MH  - Neoplastic Stem Cells/drug effects
MH  - Phytochemicals/isolation & purification/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC7866203
OTO - NOTNLM
OT  - epithelial-mesenchymal transition (EMT)
OT  - lung cancer
OT  - metastasis
OT  - migration
OT  - ovalitenone
COIS- The authors declare no conflict of interest.
EDAT- 2021/02/04 06:00
MHDA- 2021/09/07 06:00
PMCR- 2021/01/26
CRDT- 2021/02/03 01:02
PHST- 2020/12/24 00:00 [received]
PHST- 2021/01/22 00:00 [revised]
PHST- 2021/01/24 00:00 [accepted]
PHST- 2021/02/03 01:02 [entrez]
PHST- 2021/02/04 06:00 [pubmed]
PHST- 2021/09/07 06:00 [medline]
PHST- 2021/01/26 00:00 [pmc-release]
AID - molecules26030638 [pii]
AID - molecules-26-00638 [pii]
AID - 10.3390/molecules26030638 [doi]
PST - epublish
SO  - Molecules. 2021 Jan 26;26(3):638. doi: 10.3390/molecules26030638.