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Chemosensitizing Effect of Saikosaponin B on B16F10 Melanoma Cells
Heyao Ma1, Satoru Yokoyama1, Ikuo Saiki1
1a Division of Pathogenic Biochemistry, Department of Bioscience , Institute of Natural Medicine, University of Toyama , Toyama , Japan.
Abstract:
Cancer cell resistance to chemotherapy is one of the obstacles for better cancer treatment, and inflammatory signaling pathways, such as NF-κB signaling pathway, have been recognized to be involved in such chemoresistance. In this study, we aim to identify a new approach for overcoming cancer chemoresistance by using natural compounds. As a result of screening by using Murine B16F10 melanoma cell line constitutively expressing NF-κB luciferase reporter gene, we identified Saikosaponin B2 as an effective inhibitor for etoposide-induced NF-κB activation in B16F10NFkB cells. Saikosaponin B2 sensitized etoposide-induced cell death in B16F10 melanoma cells through the induction of apoptosis. Along with apoptosis induction, we observed an induction of γ-H2AX expression, which is a molecular signature for DNA damage, upon the combination treatment of etoposide and Saikosaponin B2. Among Saikosaponin family compounds, we found that Saikosaponin B1, but not Saikosaponin A, sensitized etoposide-induced cytotoxicity implicating the structural requirement of Saikosaponin B for such chemosensitization. By testing the combination of Saikosaponin B1 and B2 with 9 clinical anticancer drugs, Saikosaponin B showed a certain preference in the combination with those tested anticancer drugs. Collectively, we conclude Saikosaponin B can be an attractive adjuvant for enhancing the clinical effect of cancer chemotherapy.
Insights
Natural compound Saikosaponin B2 inhibits NF-κB activation, enhancing chemotherapy effectiveness. It sensitizes cancer cells to etoposide by inducing apoptosis and DNA damage, offering a promising adjuvant for cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Chemotherapy resistance in cancer is a major clinical challenge.
- Inflammatory pathways, including the NF-κB signaling pathway, are implicated in chemoresistance.
- Natural compounds offer potential strategies to overcome cancer treatment resistance.
Purpose of the Study:
- To identify natural compounds that can overcome cancer chemoresistance.
- To investigate the mechanism by which Saikosaponin B2 affects chemoresistance.
- To evaluate the potential of Saikosaponin B family compounds as chemosensitizers.
Main Methods:
- Screening of natural compounds using a Murine B16F10 melanoma cell line with a constitutively expressing NF-κB luciferase reporter gene.
- Assessing the effect of Saikosaponin B2 on etoposide-induced NF-κB activation and cell death.
- Analyzing apoptosis induction and DNA damage marker (γ-H2AX) expression.
- Evaluating Saikosaponin B1 and B2 in combination with clinical anticancer drugs.
Main Results:
- Saikosaponin B2 effectively inhibited etoposide-induced NF-κB activation in B16F10 melanoma cells.
- Saikosaponin B2 sensitized melanoma cells to etoposide-induced cell death via apoptosis.
- Combination treatment induced DNA damage, evidenced by γ-H2AX expression.
- Saikosaponin B1, but not Saikosaponin A, also sensitized cells to etoposide, suggesting a structural requirement for Saikosaponin B.
- Saikosaponin B demonstrated a preference for combination with certain clinical anticancer drugs.
Conclusions:
- Saikosaponin B2 is a potent inhibitor of NF-κB activation and sensitizes cancer cells to chemotherapy.
- Saikosaponin B compounds show potential as adjuvants to enhance the efficacy of clinical cancer chemotherapy.
- Further investigation into Saikosaponin B as a chemosensitizer is warranted for clinical application.
