PMID- 35684419
OWN - NLM
STAT- MEDLINE
DCOM- 20220613
LR  - 20220716
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 11
DP  - 2022 May 28
TI  - Targeting Akt/NF-kappaB/p53 Pathway and Apoptosis Inducing Potential of 
      1,2-Benzenedicarboxylic Acid, Bis (2-Methyl Propyl) Ester Isolated from Onosma 
      bracteata Wall. against Human Osteosarcoma (MG-63) Cells.
LID - 10.3390/molecules27113478 [doi]
LID - 3478
AB  - Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. 
      This plant is commonly used in the preparation of traditional Ayurvedic drugs to 
      treat numerous diseases. Inspired by the medicinal properties of this plant, the 
      present study aimed to investigate the antiproliferative potential and the 
      primary molecular mechanisms of the apoptotic induction against human 
      osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata, 
      ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide 
      radical scavenging assay and lipid peroxidation assay with an EC(50) value of 
      95.12 and 80.67 microg/mL, respectively. Silica gel column chromatography of ethyl 
      acetate (Obea) fraction of O. bracteata yielded a pure compound, which was 
      characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene 
      dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was 
      evaluated for the antiproliferative potential against human osteosarcoma MG-63, 
      human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay 
      and exhibited GI(50) values of 37.53 muM, 56.05 muM, and 47.12 muM, respectively. In 
      MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously 
      decreased the mitochondria membrane potential (MMP) potential by arresting cells 
      at the G(0)/G(1) phase, suggesting the initiation of apoptosis. Western blotting 
      analysis revealed the upregulation of p53, caspase3, and caspase9 while the 
      expressions of p-NF-kappaB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also 
      showed upregulation in the expression of p53 and caspase3 and downregulation in 
      the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis 
      displayed the interaction between BDCe fraction with p53 (-151.13 kcal/mol) and 
      CDK1 (-133.96 kcal/mol). The results of the present work suggest that the BDCe 
      fraction has chemopreventive properties against osteosarcoma (MG-63) cells 
      through the induction of cell cycle arrest and apoptosis via Akt/NF-kappaB/p53 
      pathways. This study contributes to the understanding of the utilization of BDCe 
      fraction in osteosarcoma treatment.
FAU - Kumar, Ajay
AU  - Kumar A
AD  - Department of Botanical and Environmental Sciences, Guru Nanak Dev University, 
      Amritsar 143005, India.
FAU - Kaur, Sandeep
AU  - Kaur S
AD  - Department of Botanical and Environmental Sciences, Guru Nanak Dev University, 
      Amritsar 143005, India.
FAU - Dhiman, Sukhvinder
AU  - Dhiman S
AUID- ORCID: 0000-0001-7466-975X
AD  - Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
FAU - Singh, Prithvi Pal
AU  - Singh PP
AD  - Chemical Technology Division, CSIR-IHBT, Palampur 176061, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
FAU - Bhatia, Gaurav
AU  - Bhatia G
AD  - Department of Biochemistry, Pt. Jawaharlal Nehru Government Medical College and 
      Hospital Chamba, Chamba 176310, India.
FAU - Thakur, Sharad
AU  - Thakur S
AD  - Biotechnology Division, COVID-19 Project, CSIR-IHBT, Palampur 176061, India.
FAU - Tuli, Hardeep Singh
AU  - Tuli HS
AUID- ORCID: 0000-0003-1155-0094
AD  - Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), 
      Mullana, Ambala 133207, India.
FAU - Sharma, Upendra
AU  - Sharma U
AUID- ORCID: 0000-0002-7693-8690
AD  - Chemical Technology Division, CSIR-IHBT, Palampur 176061, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
FAU - Kumar, Subodh
AU  - Kumar S
AD  - Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
FAU - Almutary, Abdulmajeed G
AU  - Almutary AG
AUID- ORCID: 0000-0001-5709-4130
AD  - Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim 
      University, Buraydah 52266, Saudi Arabia.
FAU - Alnuqaydan, Abdullah M
AU  - Alnuqaydan AM
AUID- ORCID: 0000-0001-9306-609X
AD  - Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim 
      University, Buraydah 52266, Saudi Arabia.
FAU - Hussain, Arif
AU  - Hussain A
AUID- ORCID: 0000-0002-0851-4845
AD  - School of Life Sciences, Manipal Academy of Higher Education, Dubai Campus, Dubai 
      345050, United Arab Emirates.
FAU - Haque, Shafiul
AU  - Haque S
AUID- ORCID: 0000-0002-2989-121X
AD  - Research and Scientific Studies Unit, College of Nursing and Allied Health 
      Sciences, Jazan University, Jazan 45142, Saudi Arabia.
AD  - Bursa Uludag University Faculty of Medicine, Gorukle Campus, 16059 Nilufer, 
      Turkey.
FAU - Dhama, Kuldeep
AU  - Dhama K
AUID- ORCID: 0000-0001-7469-4752
AD  - Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 
      243122, India.
FAU - Kaur, Satwinderjeet
AU  - Kaur S
AD  - Department of Botanical and Environmental Sciences, Guru Nanak Dev University, 
      Amritsar 143005, India.
LA  - eng
GR  - NA/Qassim University/
PT  - Journal Article
DEP - 20220528
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Esters)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Apoptosis
MH  - *Bone Neoplasms
MH  - *Boraginaceae/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Esters
MH  - Humans
MH  - Molecular Docking Simulation
MH  - NF-kappa B/metabolism
MH  - *Osteosarcoma/drug therapy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC9182111
OTO - NOTNLM
OT  - G0/G1 phase
OT  - Onosma bracteata
OT  - ROS
OT  - antiproliferative activity
OT  - apoptosis induction
OT  - osteosarcoma
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/11 06:00
MHDA- 2022/06/14 06:00
PMCR- 2022/05/28
CRDT- 2022/06/10 01:24
PHST- 2022/04/08 00:00 [received]
PHST- 2022/05/15 00:00 [revised]
PHST- 2022/05/18 00:00 [accepted]
PHST- 2022/06/10 01:24 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/14 06:00 [medline]
PHST- 2022/05/28 00:00 [pmc-release]
AID - molecules27113478 [pii]
AID - molecules-27-03478 [pii]
AID - 10.3390/molecules27113478 [doi]
PST - epublish
SO  - Molecules. 2022 May 28;27(11):3478. doi: 10.3390/molecules27113478.