PMID- 32521922
OWN - NLM
STAT- MEDLINE
DCOM- 20210208
LR  - 20210208
IS  - 2241-6293 (Electronic)
IS  - 1107-0625 (Linking)
VI  - 25
IP  - 2
DP  - 2020 Mar-Apr
TI  - Anticancer effects of Mahanimbine alkaloid on the human bladder cancer cells are 
      due to the induction of G0/G1 cell cycle arrest, apoptosis and autophagy.
PG  - 1166-1171
AB  - PURPOSE: The main purpose of the current research work was to investigate the 
      anticancer effects of Mahanimbine alkaloid in human bladder cancer cells along 
      with examining its effects on cellular apoptosis, cell cycle phase distribution, 
      and cell autophagy. METHODS: Cell viability was examined by WST-1 cell viability 
      assay. Mahanimbine-induced apoptosis was examined by fluorescent microscopy using 
      acridine orange (AO)/ethidium bromide (EB) staining as well as using flow 
      cytometry in combination with annexin-v/propidium iodide (PI) staining. Further, 
      western blot assay was used to study the effects of Mahanimbine on 
      apoptosis-related protein expressions including Bax and Bcl-2. Autophagy 
      induction was evaluated by transmission electron microscopy (TEM) and western 
      blot. Flow cytometry was used to study the effects on cell cycle. RESULTS: The 
      results showed that Mahanimbine decreased the viability of the human bladder 
      cancer cells and exhibited an IC50 of 32.5 microM. The test molecule also caused 
      remarkable changes in the morphology of human bladder cancer cells and inhibited 
      their colony forming potential. The AO/EB staining assay showed that Mahanimbine 
      inhibits the viability of cancer cells via induction of apoptotic cell death 
      which was associated with increase in Bax and decrease in Bcl-2 levels. The 
      apoptotic cells increased from 5.2% in control to around 75% at 100 microM 
      concentration. Mahanimbine also led to dose-dependent G0/G1 cell cycle arrest. 
      Autophagic vacuoles appeared in the treated cells indicating autophagic induction 
      by the test molecule. The Mahanimbine-triggered autophagy was also linked with 
      increase in the expression of LC3II and decrease in p62 expression. However, no 
      apparent effects were observed on the LC3 I expression. CONCLUSION: Taken 
      together, the results of this study indicate that Mahanimbine natural product has 
      the potential to be developed as a promising anticancer agent against human 
      bladder carcinoma but further studies are needed to this direction.
FAU - Xie, Huang
AU  - Xie H
AD  - Department of Urinary Surgery, the second affiliated Hospital, University of 
      South China, Hengyang, Hunan, China.
FAU - Zhang, Tao
AU  - Zhang T
FAU - Yang, Ning
AU  - Yang N
FAU - Li, Zhijun
AU  - Li Z
FAU - Liu, Yimin
AU  - Liu Y
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 (Alkaloids)
RN  - 0 (Carbazoles)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (mahanimbine)
SB  - IM
MH  - Alkaloids/pharmacology/*therapeutic use
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Carbazoles/pharmacology/*therapeutic use
MH  - Cell Cycle Checkpoints/*genetics
MH  - Heterocyclic Compounds, 4 or More Rings/pharmacology/*therapeutic use
MH  - Humans
MH  - Urinary Bladder Neoplasms/*drug therapy
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):1166-1171.