Annosquacin B induces mitochondrial apoptosis in multidrug resistant human breast cancer cell line MCF-7/ADR through
Fei Yuan1,2, Ganggang Bai1,3, Yunjie Miao1
1a College of Pharmacy, Nanjing University of Chinese Medicine , Nanjing , China.
Context:
Multidrug resistance (MDR) is a major obstacle to efficient therapy of cancers. It is a prime concern for researchers to find compounds with anti-proliferative activity on MDR cell lines. In recent years, annonaceous acetogenins (ACGs) were reported to have anti-proliferative activity. However, the underlying mechanisms are still unknown.
Objective:
This study determines the mechanisms of anti-proliferative activity induced by Annosquacin B (AB) against MCF-7/ADR cells.
Material And Methods:
The cytotoxicity of AB at varying concentrations (0.64, 1.6, 4, 10, 25, 62.5, 156.25 μM) on MCF-7/ADR cells was assessed using the MTT assay. Annexin V-FITC/propidium iodide staining and Acrinidine orange and ethidium bromide (AO/EB) staining were employed to investigate whether AB (14, 7, 3.5 μM) could induce apoptosis in MCF-7/ADR cells. Levels of caspase-3 and caspase-9, Bax, Bcl-2 and MAPKs kinases were evaluated by western blot assay following treatment with various concentrations of AB (3.5, 7, 14 μM) at different time points (0, 0.5, 1, 2, 4, 8, 12 h).
Results And Conclusion:
MTT assay showed that AB significantly decreased cell viability on MCF-7/ADR (IC50 of 14.69 μM). AB-induced apoptosis in MCF-7/ADR cells through mitochondrial apoptosis pathways. It induced typical apoptosis by morphologic changes; elevate levels of caspase-3, caspase-9 as well as the ratio of Bax/Bcl-2. In addition, AB increased the expression of p-p38 MAPK and decreased the expression of p-JNK, while whether ERK1/2 had an effect on the MCF-7/ADR apoptosis remains to be determined.
Insights
Annosquacin B (AB) effectively combats multidrug resistance (MDR) in cancer by inducing apoptosis in resistant cells. This compound triggers programmed cell death through mitochondrial pathways, offering a potential new avenue for cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) significantly hinders cancer treatment efficacy.
- Annonaceous acetogenins (ACGs) show potential anti-proliferative effects against MDR cell lines, but their mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which Annosquacin B (AB) exerts its anti-proliferative effects on MCF-7/ADR cells.
Main Methods:
- Cytotoxicity was assessed using MTT assays.
- Apoptosis induction was evaluated via Annexin V-FITC/propidium iodide and AO/EB staining.
- Western blot analysis was performed to measure levels of apoptosis-related proteins (caspase-3, caspase-9, Bax, Bcl-2) and MAPKs.
Main Results:
- Annosquacin B demonstrated significant cytotoxicity against MCF-7/ADR cells with an IC50 of 14.69 μM.
- AB treatment induced apoptosis in MCF-7/ADR cells, evidenced by morphological changes and altered protein expression.
- Key apoptotic markers, including elevated caspase-3, caspase-9, and an increased Bax/Bcl-2 ratio, were observed.
Conclusions:
- Annosquacin B induces apoptosis in multidrug-resistant MCF-7/ADR cells via the mitochondrial pathway.
- AB modulates MAPK signaling, upregulating p-p38 MAPK and downregulating p-JNK.
- Further investigation is needed to determine the role of ERK1/2 in AB-induced apoptosis.
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