Ilimaquinone Induces Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma Cells
Cheng-Wen Lin1,2, Li-Yuan Bai3,4, Jui-Hsin Su5
1Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan.
Abstract:
In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC50 values of 7.5 and 8.5 μM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ's anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy.
Insights
Ilimaquinone (IQ), a marine sponge compound, effectively reduced oral squamous cell carcinoma (OSCC) cell viability. IQ triggers apoptosis and protective autophagy, showing potential for OSCC cancer therapy.
Area of Science:
- Marine Natural Products
- Cancer Biology
- Pharmacology
Background:
- Oral squamous cell carcinoma (OSCC) is a significant global health concern.
- Marine natural products offer a promising source for novel anti-cancer agents.
- Ilimaquinone (IQ) is a sesquiterpene quinone isolated from the marine sponge *Halichondria* sp.
Purpose of the Study:
- To investigate the anti-tumor activity of ilimaquinone (IQ) in oral squamous cell carcinoma (OSCC) cells.
- To elucidate the mechanisms underlying IQ's anti-cancer effects, including apoptosis and autophagy induction.
Main Methods:
- Cell viability assays (IC50 determination) on OSCC cell lines (SCC4, SCC2095).
- Flow cytometry to analyze apoptosis and reactive oxygen species (ROS) generation.
- Western blotting to assess protein expression (Akt, p38, Mcl-1, p53, LC3B-II, Atg5).
- Gene knockdown (p53) and use of autophagy inhibitors (3-methyladenine, chloroquine).
Main Results:
- IQ significantly suppressed OSCC cell viability with IC50 values of 7.5 μM (SCC4) and 8.5 μM (SCC2095).
- IQ induced caspase-dependent apoptosis and modulated key cell growth regulators (Akt, p38, Mcl-1, p53).
- IQ triggered ROS generation and protective autophagy, evidenced by organelle changes and protein expression.
Conclusions:
- Ilimaquinone exhibits potent anti-tumor activity against OSCC cells.
- IQ's mechanism involves inducing apoptosis and protective autophagy, modulated by p53 and ROS.
- IQ demonstrates potential as a therapeutic agent for oral squamous cell carcinoma.
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