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Updated: Feb 8, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Nitidine chloride represses Mcl-1 protein via lysosomal degradation in oral squamous cell carcinoma
In-Hyoung Yang1, Won Jung2, Lee-Han Kim1
1Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
Background:
We have shown previously that nitidine chloride (NC) induces apoptosis via inhibition of signal transducer and activator of transcription 3 (STAT3). However, its downstream molecules are not fully understood yet. Here, we report that NC as STAT3 inhibitor downregulates myeloid cell leukemia-1 (Mcl-1) protein in HSC-3 and HSC-4 human oral squamous cell carcinoma (OSCC) cells and a nude mouse tumor xenograft model.
Methods:
This study investigated the effects of NC on Mcl-1 expression in HSC-3 and HSC-4 cells using Western blotting, RT-PCR, and dual-luciferase assay. Immunohistochemistry was employed to evaluate Mcl-1 expression levels in mouse tumor tissues. Construction of Mcl-1 overexpression vector and transient transfection was done to test the apoptosis of HSC-3 cells.
Results:
Nitidine chloride did not affect either mRNA level or promoter activity of Mcl-1, and the decrease in Mcl-1 protein by NC was caused by lysosome-dependent degradation, but not proteasome-dependent degradation. The overexpression of Mcl-1 protein in OSCC cell lines was sufficient to block the induction of apoptosis. In addition, NC strongly reduced the expression level of Mcl-1 protein compared with other STAT3 inhibitors such as cryptotanshione and S3I-201 in OSCCs.
Conclusions:
Our findings suggest that NC triggers apoptosis via lysosome-dependent Mcl-1 protein degradation and could be chosen as a promising chemotherapeutic candidate against human OSCCs.
Insights
Nitidine chloride (NC) triggers apoptosis in oral squamous cell carcinoma (OSCC) by degrading myeloid cell leukemia-1 (Mcl-1) protein through lysosomes. This suggests NC is a promising candidate for OSCC chemotherapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Nitidine chloride (NC) is known to induce apoptosis by inhibiting signal transducer and activator of transcription 3 (STAT3).
- The precise downstream molecular mechanisms of NC-induced apoptosis remain incompletely understood.
- This study investigates the effect of NC on myeloid cell leukemia-1 (Mcl-1) expression in oral squamous cell carcinoma (OSCC).
Purpose of the Study:
- To elucidate the role of Mcl-1 in NC-induced apoptosis in OSCC.
- To determine the mechanism by which NC affects Mcl-1 protein levels.
- To evaluate the therapeutic potential of NC against OSCC.
Main Methods:
- Investigated NC effects on Mcl-1 expression in HSC-3 and HSC-4 cells using Western blotting, RT-PCR, and dual-luciferase assays.
- Utilized immunohistochemistry to assess Mcl-1 levels in mouse tumor xenografts.
- Employed Mcl-1 overexpression vectors and transient transfection to study apoptosis induction.
Main Results:
- NC-induced decrease in Mcl-1 protein levels is mediated by lysosome-dependent degradation, not proteasome-dependent degradation.
- Overexpression of Mcl-1 protein abrogated NC-induced apoptosis in OSCC cell lines.
- NC demonstrated a stronger reduction in Mcl-1 protein compared to other STAT3 inhibitors in OSCC.
Conclusions:
- NC induces apoptosis in OSCC through lysosome-dependent degradation of Mcl-1 protein.
- NC exhibits potential as a chemotherapeutic agent for human OSCC.
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