Protopanaxadiol Induces Apoptosis in NPC/HK1 Human Nasopharyngeal Carcinoma Cells via the Fas/Caspase-8 Signaling
Yaw-Chang Huang1,2, Chih-Chun Wang1,2, Chuanchien Yang1,2
1School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan, R.O.C.
Background/Aim:
Nasopharyngeal carcinoma (NPC) originates in the nasopharynx. Despite therapeutic advances, a subset of patients derives limited benefits and experiences poor outcomes. There is a continuing need for novel agents to improve prognosis.
Materials And Methods:
Human immortalized nasopharyngeal epithelial cells (NP69) and NPC cells (NPC/HK1) were used. Cell viability, clonogenic growth, cytokeratin-18 fragment levels, and protein expression were assessed by MTT assay, colony formation assay, ELISA, and immunoblotting, respectively.
Results:
Protopanaxadiol reduced NPC/HK1 cell viability in a concentration-dependent manner without significantly affecting NP69 cells and markedly suppressed NPC/HK1 colony formation. Treatment with protopanaxadiol increased the cleaved PARP and cytokeratin-18 fragments, without significant changes in Beclin-1 or LC3-II, suggesting that apoptosis rather than autophagy occurred. Additionally, protopanaxadiol reduced ERK phosphorylation while increasing both total and phosphorylated p53 levels. It also up-regulated Fas and elevated levels of cleaved caspase-8 and cleaved caspase-3, whereas cleaved caspase-9 and Bax remained largely unchanged, indicating a preferential activation of the extrinsic apoptotic pathway. Functionally, blocking Fas or caspase-8 attenuated protopanaxadiol-induced cytokeratin-18 fragment release.
Conclusion:
Protopanaxadiol selectively suppresses NPC/HK1 growth, induces apoptotic markers, and promotes apoptosis via the Fas/caspase-8 signaling pathway. These findings provide foundational evidence that protopanaxadiol is a promising candidate to improve NPC therapy.
Insights
Protopanaxadiol selectively inhibits nasopharyngeal carcinoma (NPC) cell growth by inducing apoptosis through the Fas/caspase-8 pathway. This natural compound shows promise as a novel therapeutic agent for NPC patients with poor outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Nasopharyngeal carcinoma (NPC) presents therapeutic challenges, with many patients experiencing limited benefit and poor prognosis.
- Novel therapeutic agents are crucial to enhance treatment outcomes for NPC patients.
Purpose of the Study:
- To investigate the anti-cancer effects of protopanaxadiol on nasopharyngeal carcinoma (NPC) cells.
- To elucidate the underlying mechanisms of protopanaxadiol-induced cell death in NPC.
Main Methods:
- Cell viability and clonogenic growth were assessed using MTT and colony formation assays.
- Apoptosis and autophagy markers (cleaved PARP, cytokeratin-18, Beclin-1, LC3-II) were evaluated.
- Protein expression (ERK, p53, Fas, caspase-8, caspase-3, caspase-9, Bax) and signaling pathways were analyzed via immunoblotting.
Main Results:
- Protopanaxadiol reduced NPC cell viability and colony formation without affecting normal nasopharyngeal cells.
- Apoptosis, indicated by increased cleaved PARP and cytokeratin-18, was induced, while autophagy markers remained unchanged.
- Protopanaxadiol activated the extrinsic apoptotic pathway via Fas/caspase-8, decreasing ERK phosphorylation and increasing p53 levels.
Conclusions:
- Protopanaxadiol exhibits selective anti-cancer activity against NPC cells.
- The compound effectively induces apoptosis through the Fas/caspase-8 signaling pathway.
- Protopanaxadiol represents a promising therapeutic candidate for improving nasopharyngeal carcinoma treatment.
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