PMID- 36281695
OWN - NLM
STAT- MEDLINE
DCOM- 20221116
LR  - 20240102
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 13
IP  - 22
DP  - 2022 Nov 14
TI  - Antiproliferative potential of Physalis peruviana-derived magnolin against 
      pancreatic cancer: a comprehensive in vitro and in silico study.
PG  - 11733-11743
LID - 10.1039/d2fo01915a [doi]
AB  - Physalis peruviana L. is a common edible fruit in Egypt and other regional 
      countries. In the present study, we investigated its crude extract as a potential 
      source of antiproliferative secondary metabolites. Upon bioactivity guided 
      solvent fractionation, ethyl acetate extract showed preferential activity toward 
      the human pancreatic cancer cell line PANC-1 with an IC(50) value of 5.23 +/- 0.2 
      mug mL(-1). The subsequent HR-LCMS-guided and biological activity-guided isolation 
      revealed magnolin as a potent preferential antiproliferative agent against PANC-1 
      with an IC(50) of 0.51 +/- 0.46 muM that was comparable to that of the positive 
      control doxorubocin (IC(50) of 0.17 +/- 0.15 muM). Moreover, magnolin showed much 
      less cytotoxicity in comparison with the positive control doxorubicin (6.96% and 
      30.48% growth inhibition, respectively, at 5 mug mL(-1)) towards normal human 
      cells (i.e. dermal fibroblasts; HDFa). Furthermore, magnolin was able to induce a 
      concentration-dependent suppression of the formation of PANC-1 colonies, where 
      the treatment of the tumor cells with 25 nM, 50 nM, and 100 nM concentrations of 
      the compound resulted in a 36%, 57, and 78% reduction, respectively, in the 
      PANC-1 colony formation. Additionally, magnolin was observed to limit PANC-1 
      tumor cell migration in the tumor cell wound healing assay, indicating a 
      substantial anti-migratory effect against the PANC-1 cell line. A subsequent in 
      silico-based study of this compound structure putatively suggested matrix 
      metalloproteinase-3 (MMP3) as the molecular target that mediates these observed 
      effects on PANC-1 cells. Absolute binding free energy estimation (DeltaG(binding)) 
      and 100 ns long molecular dynamics simulation (MDS) experiments indicated that 
      the magnolin structure has good affinity towards the MMP3's active site and can 
      achieve significantly stable binding inside it. Accordingly, upon experimental 
      validation, magnolin was found to inhibit the catalytic activity of MMP3 in a 
      dose-dependent manner with a nanomolar IC(50) value of 185 nm +/- 4.86 and a K(i) 
      of 112 nm +/- 6.31. In conclusion, our results clearly revealed that magnolin 
      derived from P. peruviana is an interesting antiproliferative and antimetastatic 
      agent against PANC-1 cells with potent inhibitory activity against MMP3. Further 
      in vivo evaluation will be of great interest in the future.
FAU - Sayed, Ahmed M
AU  - Sayed AM
AUID- ORCID: 0000-0002-1442-183X
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 
      62513, Egypt.
FAU - El-Hawary, Seham S
AU  - El-Hawary SS
AD  - Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
FAU - Abdelmohsen, Usama Ramadan
AU  - Abdelmohsen UR
AUID- ORCID: 0000-0002-1014-6922
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, 
      Egypt.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 
      61111, Egypt.
FAU - Ghareeb, Mosad A
AU  - Ghareeb MA
AUID- ORCID: 0000-0002-8398-1937
AD  - Medicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish 
      El-Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. 
      m.ghareeb@tbri.gov.eg.
LA  - eng
PT  - Journal Article
DEP - 20221114
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 31008-18-1 (magnolin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 0 (Lignans)
SB  - IM
MH  - Humans
MH  - *Physalis
MH  - Matrix Metalloproteinase 3
MH  - *Lignans/pharmacology
MH  - *Pancreatic Neoplasms/drug therapy
MH  - Cell Line, Tumor
MH  - Cell Proliferation
EDAT- 2022/10/26 06:00
MHDA- 2022/11/18 06:00
CRDT- 2022/10/25 04:12
PHST- 2022/10/26 06:00 [pubmed]
PHST- 2022/11/18 06:00 [medline]
PHST- 2022/10/25 04:12 [entrez]
AID - 10.1039/d2fo01915a [doi]
PST - epublish
SO  - Food Funct. 2022 Nov 14;13(22):11733-11743. doi: 10.1039/d2fo01915a.