PMID- 33724660
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20210727
IS  - 1099-0461 (Electronic)
IS  - 1095-6670 (Linking)
VI  - 35
IP  - 6
DP  - 2021 Jun
TI  - Phyllanthin inhibits MOLT-4 leukemic cancer cell growth and induces apoptosis 
      through the inhibition of AKT and JNK signaling pathway.
PG  - 1-10
LID - 10.1002/jbt.22758 [doi]
AB  - Among cancers, leukemia is a multistep progression that involves genetic 
      modifications of normal hematopoietic progenitor cells to cancerous cells. In 
      recent times, leukemia cases and their mortality rate have increased rapidly. 
      Therefore, the immense need for a therapeutic approach is crucial that can 
      control this type of cancer. Phyllanthin is a lignan compound constituent from 
      the Phyllanthus species and has numerous beneficial effects as a dietary 
      component. The present study aims to determine the impact of phyllanthin on the 
      MOLT-4 cytotoxic effect. MOLT-4 cells and MS-5 cells were cultured at different 
      concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 muM/ml), and the 
      viability was assessed by the 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The level of 
      reactive oxygen species, the membrane potential of mitochondria, apoptosis by 
      2',7'-dichlorofluorescin-diacetate (DCF-DA), rhodamine, acridine orange 
      (AO)/ethidium bromide (EB), 4',6-diamidino-2-phenylindole (DAPI)/propidium iodide 
      (PI) staining, gene expression of signaling molecules, and protein levels were 
      assessed by reverse-transcription polymerase chain reaction and western blot 
      analysis. Phyllanthin did not show toxicity toward MS-5 cells and significantly 
      decreased the cell viability of MOLT-4 cells with an IC(50) value of 25 microM/ml. 
      Also, phyllanthin induced the production of reactive oxygen species and led to 
      the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining 
      fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. 
      The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, 
      antiapoptotic gene Bcl-2, NF-kappaB, and TNF-alpha decreased, but the proapoptotic Bax 
      mRNA expression was increased. The phosphorylated protein levels of p-PI3K1/2, 
      p-ERK1/2, and p-AKT were decreased, whereas the levels of p-p38 and p-JNKT1/2 
      increased. Our results confirmed that phyllanthin inhibits the MOLT-4 cells, 
      increases apoptosis, and inhibits MOLT-4 migration and cell invasion. Therefore, 
      phyllanthin can be used as a potential target for leukemia treatment.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Hematology, Shaanxi Provincial People's Hospital, Xi'an, China.
FAU - Chinnathambi, Arunachalam
AU  - Chinnathambi A
AD  - Department of Botany and Microbiology, College of Science, King Saud University, 
      Riyadh, Saudi Arabia.
FAU - Alahmadi, Tahani Awad
AU  - Alahmadi TA
AD  - Department of Pediatrics, College of Medicine, King Saud University [Medical 
      City], King Khalid University Hospital, Riyadh-, Saudi Arabia.
FAU - Alharbi, Sulaiman Ali
AU  - Alharbi SA
AD  - Department of Botany and Microbiology, College of Science, King Saud University, 
      Riyadh, Saudi Arabia.
FAU - Veeraraghavan, Vishnu Priya
AU  - Veeraraghavan VP
AUID- ORCID: 0000-0002-5071-9860
AD  - Department of Biochemistry, Saveetha Dental College, Saveetha Institute of 
      Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India.
FAU - Krishna Mohan, Surapaneni
AU  - Krishna Mohan S
AUID- ORCID: 0000-0002-5204-5708
AD  - Department of Biochemistry, Clinical Skills & Simulation and Research, Panimalar 
      Medical College Hospital & Research Institute, Varadharajapuram, Poonamallee, 
      Chennai, Tamil Nadu, India.
FAU - Hussain, Sardar
AU  - Hussain S
AD  - Department of Biotechnology, Government Science College, Chitradurga, Karnataka, 
      India.
FAU - Ramamoorthy, Kavitha
AU  - Ramamoorthy K
AD  - Department of Biotechnology, Periyar University PG Extension Centre, Dharmapuri, 
      Tamil Nadu, India.
FAU - Rengarajan, Thamaraiselvan
AU  - Rengarajan T
AD  - Scigen Research and Innovation Pvt. Ltd., Periyar Technology Business Incubator, 
      Thanjavur, Tamil Nadu, India.
LA  - eng
PT  - Journal Article
DEP - 20210316
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 0 (Lignans)
RN  - 75O1TFF47Z (phyllanthin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Humans
MH  - Leukemia/drug therapy/*metabolism/pathology
MH  - Lignans/*pharmacology
MH  - MAP Kinase Kinase 4/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - AKT/JNK signaling pathway
OT  - MOLT-4 cells
OT  - apoptosis
OT  - cyclin D1
OT  - phyllanthin
EDAT- 2021/03/17 06:00
MHDA- 2021/07/28 06:00
CRDT- 2021/03/16 12:55
PHST- 2020/12/08 00:00 [revised]
PHST- 2020/08/31 00:00 [received]
PHST- 2021/01/09 00:00 [accepted]
PHST- 2021/03/17 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2021/03/16 12:55 [entrez]
AID - 10.1002/jbt.22758 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 2021 Jun;35(6):1-10. doi: 10.1002/jbt.22758. Epub 2021 Mar 
      16.