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The PI3K Inhibitor HCD Promotes Caspase Activation in Head and Neck Squamous Cells by Upregulating the Extrinsic and
Leong-Perng Chan1, Ya-Ping Tseng2, Hui-Ching Wang3
1Department of Otorhinolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Summary
16-hydroxycleroda-3,13-dien-15,16-olide (HCD) induces apoptosis in head and neck cancer cells by increasing oxidative stress and activating cell death pathways. This PI3K inhibitor shows potential for developing novel anticancer therapies.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- 16-hydroxycleroda-3,13-dien-15,16-olide (HCD), a PI3K inhibitor from *Polyalthia longifolia*, exhibits cytotoxic properties.
- PI3K signaling is crucial for apoptosis regulation in cancer cells.
Purpose of the Study:
- To investigate the apoptotic effects of HCD in head and neck cancer (oral squamous cell carcinoma - OSCC) models.
- To elucidate the molecular mechanisms underlying HCD-induced apoptosis.
Main Methods:
- OSCC cell lines (SCC25, SCC180) were treated with HCD at various concentrations and time points.
- Assessed cell viability, oxidative stress (MitoSOX, CellROX), apoptosis markers (gene/protein expression), and mitochondrial pathways.
Main Results:
- HCD induced apoptosis, increased ROS, decreased glutathione, and altered Bcl-2/Bax expression.
- Apoptosis was mediated via TNF-α/TNF-R and FasL/Fas death receptor pathways, activating caspases.
- HCD inhibited SCC25 cell growth dose-dependently, potentiating cisplatin effects.
Conclusions:
- HCD induces apoptosis in OSCC cells through oxidative stress, mitochondrial, and death receptor pathways.
- HCD demonstrates potential as an anticancer therapeutic agent for head and neck cancers.
- Further research into HCD's molecular mechanisms can guide novel anticancer drug development.
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