PUBLICATION
A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model
- Authors
- Hu, M., Varier, K.M., Li, Z., Qin, X., Rao, Q., Song, J., Hu, A., Hang, Y., Yuan, C., Gajendran, B., Shu, L., Wen, M., Li, Y., Liu, H.
- ID
- ZDB-PUB-210730-14
- Date
- 2021
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 141: 111877 (Journal)
- Registered Authors
- Shu, Li-Ping
- Keywords
- Acylphloroglucinol, Anti-angiogenesis, Flk-1, HEL cells, Intrinsic apoptotic pathway, STAT3
- MeSH Terms
-
- Angiogenesis Inhibitors/isolation & purification
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents, Phytogenic/isolation & purification
- Antineoplastic Agents, Phytogenic/pharmacology
- Cell Line, Tumor
- Cell Proliferation/drug effects*
- Cell Proliferation/physiology
- Dose-Response Relationship, Drug
- Hep G2 Cells
- Humans
- Phloroglucinol/isolation & purification
- Phloroglucinol/pharmacology*
- Plant Extracts/isolation & purification
- Plant Extracts/pharmacology*
- Protein Structure, Secondary
- STAT3 Transcription Factor/antagonists & inhibitors*
- STAT3 Transcription Factor/metabolism
- Signal Transduction/drug effects*
- Signal Transduction/physiology
- Zebrafish
- PubMed
- 34323693 Full text @ Biomed. Pharmacother.
Citation
Hu, M., Varier, K.M., Li, Z., Qin, X., Rao, Q., Song, J., Hu, A., Hang, Y., Yuan, C., Gajendran, B., Shu, L., Wen, M., Li, Y., Liu, H. (2021) A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 141:111877.
Abstract
Leukemia is responsible for a reason of death, globally. Even though there are several treatment regimens available in the clinics against this disease, a perfect chemotherapeutic agent for the same is still under investigation. Natural plant-derived secondary metabolites are used in clinics to treat leukemia for better benefits with reduced side-effects. Likely, several bioactive compounds from Callistemon sp. were reported for their bioactive benefits. Furthermore, acylphloroglucinol derivatives from Callistemon salignus, showed both antimicrobial and cytotoxic activities in various adherent human cancer cell lines. Thus, in the present study, a natural acylphloroglucinol (2,6-dihydroxy-4-methoxyisobutyrophenone, L72) was tested for its antiproliferative efficacy in HEL cells. The MTT and the cell cycle analysis study revealed that L72 treatment can offer antiproliferative effects, both time and dose-dependent manner, causing G2/M cell cycle arrest. The western blot analysis revealed that L72 treatment triggered intrinsic apoptotic machinery and activated p21. Likewise, L72 could downregulate the gene expressions of XIAP, FLT3, IDH2, and SOD2, which was demonstrated by qPCR analysis, thus promoting its antiproliferative action. The L72 could impede STAT3 expression, which was evidenced by insilico autodock analysis and western blot analysis using STAT3 inhibitor, Pimozide. The treatment of transgenic (Flk-1+/egfr+) zebrafish embryos resulted in the STAT3 gene inhibition, proving its anti-angiogenic effect, as well. Thus, the study revealed that L72 could act as an antiproliferative agent, by triggering caspase-dependent intrinsic apoptosis, reducing cell proliferation by attenuating STAT3, and activating an anti-angiogenic pathway via Flk-1inhibition.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping