PMID- 32521863
OWN - NLM
STAT- MEDLINE
DCOM- 20210208
LR  - 20231213
IS  - 2241-6293 (Electronic)
IS  - 1107-0625 (Linking)
VI  - 25
IP  - 2
DP  - 2020 Mar-Apr
TI  - Anticancer activity of ursolic acid on human ovarian cancer cells via ROS and MMP 
      mediated apoptosis, cell cycle arrest and downregulation of PI3K/AKT pathway.
PG  - 750-756
AB  - PURPOSE: Ovarian cancer (OC) is perhaps the most difficult problem in 
      gynaecologic oncology; in particular the drug-resistant ovarian cancer remains a 
      challenge for the clinicians. Therefore there is a pressing need for novel and 
      effective chemotherapeutic agents against OC. The main objective of the current 
      research work was to study the anticancer effects of a naturally occurring 
      triterpene acid, ursolic acid, against SKOV-3 OC cells. Its effects on reactive 
      oxygen species (ROS)-mediated apoptosis were also studied along with cell cycle 
      phase distribution and PI3K/AKT signalling pathway. METHODS: Cell proliferation 
      was checked by CCK8 cell viability assay. Apoptosis-related studies were examined 
      by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) and 
      DAPI staining as well as flow cytometry using annexin V/propidium iodide (PI) 
      assay. Further, western blot assay was used to study effects of ursolic acid on 
      the apoptosis-related protein expressions including Bax, Bcl-2 as well as 
      PI3K/AKT signalling pathway. Effects on cell cycle were examined by flow 
      cytometry while effects on ROS production were evaluated by fluorescent 
      microscopy. RESULTS: Ursolic acid caused significant reduction in the viability 
      of the SKOV-3 ovarian carcinoma cells in a dose-dependent manner, exhibiting an 
      IC50 of 35 microM in cancer cells and IC50 of 75 microM in normal cell lines (normal 
      ovarian surface epithelial (OSE). Ursolic acid inhibited the viability of cancer 
      cells via induction of apoptotic cell death which was associated with increase in 
      Bax and decrease in Bcl-2 levels. DAPI staining results also confirmed that 
      ursolic acid induced apoptotic cell death. Ursolic acid also induced 
      dose-dependent G2/M phase cell cycle arrest along with causing significant 
      upsurge in ROS production. Western blot analysis revealed that ursolic acid had 
      the potential to inhibit I3K/AKT signalling pathway. CONCLUSION: The results of 
      this study clearly indicate that ursolic acid has the potential to be developed 
      as a potent drug candidate against OC provided further in vivo and toxicological 
      studies are carried out.
FAU - Lin, Wumei
AU  - Lin W
AD  - Department of Gynecology, Guangdong Academy of Medical Sciences, Guangdong 
      Provincial People's Hospital, Guangzhou, 510080, China.
FAU - Ye, Haiyan
AU  - Ye H
LA  - eng
PT  - Journal Article
PL  - Cyprus
TA  - J BUON
JT  - Journal of B.U.ON. : official journal of the Balkan Union of Oncology
JID - 100883428
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Triterpenes)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Matrix Metalloproteinases/*metabolism
MH  - Ovarian Neoplasms/*drug therapy/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/drug effects
MH  - Triterpenes/*pharmacology
MH  - Ursolic Acid
EDAT- 2020/06/12 06:00
MHDA- 2021/02/09 06:00
CRDT- 2020/06/12 06:00
PHST- 2020/06/12 06:00 [entrez]
PHST- 2020/06/12 06:00 [pubmed]
PHST- 2021/02/09 06:00 [medline]
PST - ppublish
SO  - J BUON. 2020 Mar-Apr;25(2):750-756.