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Isochamanetin is a Selective Inhibitor for CyclinD1 in SKOV3 Cell Lines
Y Swarnalatha1, V G Vidhya1, Annapoorni Murugan1
1a Department of Biotechnology , Sathyabama Institute of Science and Technology , Chennai , India.
Abstract:
The cyclinD1 is an emerging potent therapeutic drug target in the treatment of ovarian cancer. CyclinD1, Cdks phosphorylation regulates cell cycle and controls transcription. For this reason, CyclinD1 have been subject to extensive cell cycle- related research, and consequently various therapeutic inhibitor drugs have been developed to these protein targets. In the present study we identified that the expression levels of Bcl-2, Bax, caspase 8, 9 and cyclinD1 using Q-PCR method in SKOV3 cell lines treated with Isochamanetin. The viability and migratory inhibition ability also studied to know the mode of cell death. Further the expression levels of Bcl-2, caspase8,9, Cytochrome C and CyclinD1 were significantly down regulated in SKOV3 cancer cells treated with isochamanetin, a specific binding molecule to CyclinD1. The therapeutic molecules found by a high through put insilicoscreen of this pocket exhibit cytostatic nature and reduce protein levels of cell cycle. The novel structural site on CyclinD1, which is well conserved and inhibits the SKOV3 cells from G0-G1 to S phase cell cycle progression. The current result suggests that isochamanetin serves as potent binding agent to the cyclinD1.
Insights
Isochamanetin effectively targets cyclin D1, a key protein in ovarian cancer. This compound inhibits cancer cell growth and progression by downregulating critical proteins and halting cell cycle advancement.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cyclin D1 is a significant therapeutic target in ovarian cancer treatment.
- Dysregulation of cell cycle progression, controlled by Cyclin D1 and Cdks phosphorylation, is a hallmark of cancer.
- Existing research has focused on developing inhibitors for Cyclin D1-related targets.
Purpose of the Study:
- To investigate the effect of Isochamanetin on ovarian cancer cell line SKOV3.
- To determine the impact of Isochamanetin on the expression of key cell cycle and apoptosis-related proteins.
- To evaluate the therapeutic potential of Isochamanetin as a Cyclin D1 binding agent.
Main Methods:
- Quantitative Polymerase Chain Reaction (Q-PCR) was used to measure gene expression levels.
- SKOV3 ovarian cancer cells were treated with Isochamanetin.
- Cell viability and migratory inhibition assays were performed.
- In silico screening was employed to identify therapeutic molecules targeting Cyclin D1.
Main Results:
- Isochamanetin treatment significantly downregulated the expression of Bcl-2, Bax, caspase 8, 9, Cytochrome C, and Cyclin D1 in SKOV3 cells.
- The compound demonstrated cytostatic effects, inhibiting cell viability and migration.
- A novel, conserved structural site on Cyclin D1 was identified, which Isochamanetin binds to.
- Isochamanetin effectively inhibited G0-G1 to S phase cell cycle progression in SKOV3 cells.
Conclusions:
- Isochamanetin acts as a potent binding agent to Cyclin D1.
- The findings suggest Isochamanetin has therapeutic potential in ovarian cancer treatment by targeting Cyclin D1 and disrupting cell cycle progression.
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