Related Experiment Video
Updated: Jun 4, 2025
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Targeting hexokinase 2 to enhance anticancer efficacy of trichosanthin in HeLa and SCC25 cell models
Yan Zhou1, Maoxin Ran1, Wenying Shan1
1Faculty of Health Sciences, University of Macau, Taipa, Macau.
Background And Purpose:
Trichosanthin (TCS) is a plant-based ribosome-inactivating protein exhibiting a range of pharmacological properties, including abortifacient and anticancer. However, the routine clinical use in cancer treatment was hampered by its antigenicity. Hexokinase 2 (HK2) is a pivotal regulator of glycolysis, where aberrant expression is observed in many cancers. This study investigates the anticancer effects and mechanisms of TCS in combination with benserazide (Benz), a HK2 inhibitor, in Hela and SCC25 cancer models.
Experimental Approach:
MTT, colony-formation and cell cycle assays were performed to assess the cytotoxic effects of TCS and Benz in HeLa and SCC25 cells. Seahorse assay, western blotting, flow cytometry analysis and RNA sequencing were employed to investigate the pharmacological effects of the combo treatment. SCC25 cell xenograft mouse model was established for in vivo efficacy study.
Key Results:
Combined use of TCS and Benz exhibited synergistic anticancer effects in both Hela and SCC25 cell models. The observed synergistic effects were attributed to the modulation of glycolysis by targeting HK2, leading to reduced lactate production and increased ROS accumulation which further inhibited colony formation and cell cycle progression, as well as triggered apoptosis. Moreover, this combination effectively inhibited NFκB/ERK signalling pathways, which were found to be significantly activated upon single use of TCS. It was found that the combination significantly suppressed the tumour growth in SCC25 cell xenograft mouse model.
Conclusion:
Our findings suggested that targeting HK2 and modulating glycolysis may offer a promising avenue for improving the therapeutic outcomes of TCS-based anticancer treatments.
Insights
Combining trichosanthin (TCS) with benserazide (Benz), a Hexokinase 2 (HK2) inhibitor, shows synergistic anticancer effects by targeting glycolysis. This combination suppressed tumor growth and offers a promising strategy for cancer therapy.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Trichosanthin (TCS) is a plant-derived ribosome-inactivating protein with anticancer potential.
- TCS's clinical application is limited by its antigenicity.
- Hexokinase 2 (HK2) is crucial in cancer glycolysis and a potential therapeutic target.
Purpose of the Study:
- To investigate the combined anticancer effects of TCS and benserazide (Benz), an HK2 inhibitor.
- To elucidate the underlying mechanisms of the combination therapy in Hela and SCC25 cancer models.
- To evaluate the in vivo efficacy of the TCS-Benz combination.
Main Methods:
- Cytotoxicity was assessed using MTT, colony-formation, and cell cycle assays.
- Glycolysis modulation, apoptosis, and signaling pathways were analyzed via Seahorse assay, western blotting, and flow cytometry.
- In vivo efficacy was evaluated in a SCC25 cell xenograft mouse model.
Main Results:
- The TCS-Benz combination demonstrated synergistic anticancer effects in Hela and SCC25 cells.
- The combination modulated glycolysis, reducing lactate and increasing ROS, inhibiting proliferation and inducing apoptosis.
- Tumor growth was significantly suppressed in the xenograft mouse model.
Conclusions:
- Targeting HK2 and modulating glycolysis enhances TCS efficacy for cancer treatment.
- The TCS-Benz combination presents a promising therapeutic strategy by inhibiting key cancer pathways.
- This approach may overcome TCS antigenicity limitations and improve clinical outcomes.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:34Inhibition of Cdk Activity