PMID- 26852140
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 21
IP  - 5
DP  - 2016 May
TI  - Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 
      3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, 
      Staphylococcus sp. strain MB30.
PG  - 566-77
LID - 10.1007/s10495-016-1221-x [doi]
AB  - Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of 
      Bengal, India, exhibited antimicrobial activity against human pathogenic 
      bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic 
      tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive 
      metabolite produced by the strain MB30 was purified through silica gel column 
      chromatography and preparative HPLC. Purified metabolite was further 
      characterized by FT-IR, LC-MS and NMR analyses. On the basis of spectroscopic 
      data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, dione, 
      hexahydro 3-(2-methyl propyl) (PPDHMP). The PPDHMP exhibited in vitro anticancer 
      potential against lung (A549) and cervical (HeLa) cancer cells in a 
      dose-dependent manner with the IC50 concentration of 19.94 +/- 1.23 and 16.73 +/- 
      1.78 mug ml(-1) respectively. The acridine orange (AO)/ethidium bromide (EB) and 
      4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining of the IC50 
      concentration of PPDHMP-treated cancer cells exhibited an array of morphological 
      changes such as nuclear condensation, cell shrinkage and formation of apoptotic 
      bodies. The PPDHMP-treated cancer cells induced the progressive accumulation of 
      fragmented DNA in a time-dependent manner. Based on the flow cytometric analysis, 
      it has become evident that the compound was also effective in arresting the cell 
      cycle at G1 phase. Further, the Western blotting analysis confirmed the 
      down-regulation of cyclin-D1, cyclin dependent kinase (CDK-2), anti-apoptotic 
      Bcl-2 family proteins (Bcl-2 and Bcl-xL), activation of caspase-9 and 3 with the 
      cleavage of PARP. The PPDHMP-treated cancer cells also showed the inhibition of 
      migration and invasive capacity of cancer cells. In the present investigation, 
      for the first time, we have reported the extraction, purification and 
      characterization of an anticancer metabolite, PPDHMP from a new marine bacterium, 
      Staphylococcus sp. strain MB30.
FAU - Lalitha, P
AU  - Lalitha P
AD  - Department of Biotechnology, School of Life Sciences, Pondicherry University, 
      Pondicherry, 605014, India.
FAU - Veena, V
AU  - Veena V
AD  - Department of Biotechnology, School of Life Sciences, Pondicherry University, 
      Pondicherry, 605014, India.
FAU - Vidhyapriya, P
AU  - Vidhyapriya P
AD  - Department of Biotechnology, School of Life Sciences, Pondicherry University, 
      Pondicherry, 605014, India.
FAU - Lakshmi, Pragna
AU  - Lakshmi P
AD  - Centre for Bioinformatics, Pondicherry University, Pondicherry, India.
FAU - Krishna, R
AU  - Krishna R
AD  - Centre for Bioinformatics, Pondicherry University, Pondicherry, India.
FAU - Sakthivel, N
AU  - Sakthivel N
AD  - Department of Biotechnology, School of Life Sciences, Pondicherry University, 
      Pondicherry, 605014, India. puns2005@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Pyrazines)
RN  - 0 (Pyrroles)
RN  - 0 (hexahydro 3-(2-methylpropyl)pyrrole(1,2-a)pyrazine-1,4-dione)
SB  - IM
MH  - Antineoplastic Agents/*chemistry/isolation & purification/metabolism/pharmacology
MH  - Apoptosis Regulatory Proteins/chemistry/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - DNA Fragmentation
MH  - Geologic Sediments/microbiology
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Pyrazines/*chemistry/isolation & purification/metabolism/*pharmacology
MH  - Pyrroles/*chemistry/isolation & purification/metabolism/*pharmacology
MH  - Staphylococcus/*chemistry/isolation & purification/metabolism
MH  - Water Microbiology
OTO - NOTNLM
OT  - Antimicrobial activity
OT  - Bcl-2 family proteins
OT  - Caspase-3
OT  - Cytotoxicity
OT  - PPDHMP
OT  - Staphylococcus
EDAT- 2016/02/08 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/02/08 06:00
PHST- 2016/02/08 06:00 [entrez]
PHST- 2016/02/08 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1007/s10495-016-1221-x [pii]
AID - 10.1007/s10495-016-1221-x [doi]
PST - ppublish
SO  - Apoptosis. 2016 May;21(5):566-77. doi: 10.1007/s10495-016-1221-x.