PMID- 30273298
OWN - NLM
STAT- MEDLINE
DCOM- 20181212
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 24
DP  - 2018 Oct 1
TI  - Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by 
      Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target 
      of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 
      (STAT3) Signalling Pathways.
PG  - 6975-6983
LID - 10.12659/MSM.911013 [doi]
AB  - BACKGROUND Pancreatic cancer causes tremendous mortality across the globe mainly 
      due to late diagnosis and unavailability of efficient chemotheruptic agents. In 
      the current study the anticancer potential of a plant derived alkaloid, 
      Mahanimbine, was examined against a panel of pancreatic cancer cells. MATERIAL 
      AND METHODS The cell proliferation was determined by MTT assay. Annexin V/PI and 
      DAPI staining were performed to detect apoptosis. Cell cycle distribution was 
      investigated by flow cytometery. Cell migration was detected by wound healing 
      assay and protein expression was checked by western blotting. RESULTS The results 
      revealed that Mahanimbine could inhibit the proliferation of the all the 
      pancreatic cancer cells with lower cytoxicity against the normal cells. The IC50 
      ranged from 3.5 to 64 microM against the pancreatic cancer cell lines. The lowest 
      IC50 of 3.5 microM was observed tor the Capan-2 and SW119 pancreatic cancer cell 
      lines. The anticancer activity of Mahanimbine against the Capan-2 and SW119 cells 
      was found to be due to G0/G1 cell cycle arrest and induction of apoptosis. 
      Mahanimbine prompted apoptosis was also associated with decline in Bcl-2 and 
      enhancement of the Bax expression. Further, it was observed that Mahanimbine 
      could inhibit the AKT/mTOR and STAT3 signalling pathways in the Capan-2 and SW119 
      pancreatic cancer cells. The effects of the Mahanimbine were also examined on the 
      migration of the Capan-2 and SW119 pancreatic cancer cells. It was found that 
      Mahanimbine could inhibit the motility and migration of both the pancreatic 
      cancer cell lines. CONCLUSIONS We found that Mahanimbine inhibits the 
      proliferation of pancreatic cancer cells and as such Mahanimbine may prove 
      beneficial in the management of pancreatic cancer.
FAU - Pei, Chenlin
AU  - Pei C
AD  - Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, 
      Hunan, China (mainland).
FAU - He, Qun
AU  - He Q
AD  - Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South 
      University, Changsha, Hunan, China (mainland).
FAU - Liang, Shuai
AU  - Liang S
AD  - Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South 
      University, Changsha, Hunan, China (mainland).
FAU - Gong, Xuejun
AU  - Gong X
AD  - Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South 
      University, Changsha, Hunan, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20181001
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carbazoles)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (mahanimbine)
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  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Carbazoles/*pharmacology
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Heterocyclic Compounds, 4 or More Rings/*pharmacology
MH  - Humans
MH  - Pancreatic Neoplasms/*drug therapy/metabolism/pathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC6178883
EDAT- 2018/10/03 06:00
MHDA- 2018/12/13 06:00
PMCR- 2018/10/01
CRDT- 2018/10/02 06:00
PHST- 2018/10/02 06:00 [entrez]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2018/12/13 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - 911013 [pii]
AID - 10.12659/MSM.911013 [doi]
PST - epublish
SO  - Med Sci Monit. 2018 Oct 1;24:6975-6983. doi: 10.12659/MSM.911013.