PMID- 33277839
OWN - NLM
STAT- MEDLINE
DCOM- 20210820
LR  - 20210820
IS  - 2241-6293 (Electronic)
IS  - 1107-0625 (Linking)
VI  - 25
IP  - 5
DP  - 2020 Sep-Oct
TI  - Ambrosin sesquiterpene lactone exerts selective and potent anticancer effects in 
      drug-resistant human breast cancer cells (MDA-MB-231) through mitochondrial 
      mediated apoptosis, ROS generation and targeting Akt/beta-Catenin signaling pathway.
PG  - 2221-2227
AB  - PURPOSE: Breast cancer accounts for a significant proportion of cancer burden 
      among women world over. Concerning breast cancer treatment, there are only few 
      chemotherapeutic agents available, which also have serious side effects. The 
      present study was thus designed to explore in vitro the antitumor effects of 
      ambrosin sesquiterpene lactone against human drug-resistant breast cancer cells 
      (MDA-MB-231). METHODS: WST-1 assay was used to determine cell viability. The fact 
      that ambrosin induced apoptosis was studied through acridine orange (AO)/ethidium 
      bromide (EB) staining using fluorescence microscopy as well as using flow 
      cytometry in association with annexin-v/propidium iodide (PI) staining. 
      Furthermore, western blot assay was used to study effects of ambrosin on 
      apoptosis-related protein expressions including Bax and Bcl-2, as well as to 
      study the effects on numerous caspases and Akt/beta-Catenin Signaling Pathway. The 
      effects on reactive oxygen species (ROS) and mitochondrial membrane potential 
      (MMP) were evaluated by flow cytometry. RESULTS: The results showed that ambrosin 
      with an IC50 value of 25 microM decreased the viability of the MDA-MB-231 cells. The 
      cytotoxicity of ambrosin was also investigated on the MCF-12A normal breast cells 
      which showed that it exerted very low toxic effects on these cells. Ambrosin also 
      caused remarkable changes in the morphology and suppressed the colony forming 
      potential of MDA-MB-231 cells. The AO/EB staining assay showed that ambrosin 
      inhibits the viability of cancer cells via induction of apoptotic cell death 
      which was associated with increase in Bax and reduction in Bcl-2 levels. The 
      apoptotic cells increased from 3.5% in the controls to around 56% at 50 microM 
      concentration in the MDA-MB-231 cells. It was also seen that ambrosin treatment 
      to these cancer cells resulted in substantial suppression in MMP and remarkable 
      rise in ROS in a dose-dependent manner. This molecule also significantly 
      inhibited the Akt/beta-catenin signalling pathway by reducing the expressions of 
      phosphorylated GSK-3beta and Akt. CONCLUSIONS: Taken all together, the results of 
      our study indicate that ambrosin sesquiterpene may be developed as a promising 
      anticancer agent in human breast cancer provided further in-depth studies are 
      performed.
FAU - Fan, Shanji
AU  - Fan S
AD  - Department of Thyroid and Breast Surgery, the First Affiliated Hospital of the 
      University of South China, Hengyang, Hunan 421001, China.
FAU - Cui, Ying
AU  - Cui Y
FAU - Hu, Zecheng
AU  - Hu Z
FAU - Wang, Wenhao
AU  - Wang W
FAU - Jiang, Wujiu
AU  - Jiang W
FAU - Xu, Haifan
AU  - Xu 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)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes, Guaiane)
RN  - 0 (beta Catenin)
RN  - 6XI048644B (ambrosin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Mitochondria/*drug effects/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Sesquiterpenes, Guaiane/*pharmacology
MH  - Signal Transduction/drug effects
MH  - beta Catenin/*metabolism
EDAT- 2020/12/06 06:00
MHDA- 2021/08/21 06:00
CRDT- 2020/12/05 05:35
PHST- 2020/12/05 05:35 [entrez]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2021/08/21 06:00 [medline]
PST - ppublish
SO  - J BUON. 2020 Sep-Oct;25(5):2221-2227.