Oxysophocarpine Induces Apoptosis of Breast Cancer Cells by Inhibition of Nrf2/HO-1 Signaling Pathway

doi:10.3870/j.issn.1672-8009.2025.06.006

Abstract

Abstract: Objective To investigate the effect of oxysophocarpine on breast cancer(BC)cell proliferation,apoptosis,and oxidative stress by modulating the nuclear factor erythroid 2-related factor 2,(Nrf2)/ heme oxygenase-1(HO-1)/ NAD(P)H:quinone oxidoreductase 1(NQO1)pathway. Methods MDA-MB-231 and MCF-7 cell lines were used.Cell viability was detected by CCK-8 assay.Quantitative real-time polymerase chain reaction(qRT-PCR)or Western blotting were used to measure the expression level of proliferation-related(Survivin,Ki67,P21),apoptosis-related(cleaved caspase-3/9,Bax/Bcl-2 ratio),and Nrf2/HO-1/NQO1 pathway-related moleculars.Apoptosis and mitochondrial membrane potential were analyzed by flow cytometry.Oxidative stress markers superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA))were assessed via enzyme-linked immunosorbent assay(ELISA).Nrf2 was overexpressed in MDA-MB-231 cells to validate the Nrf2/HO-1/NQO1 pathway’s effect.A nude mouse xenograft model was established to evaluate tumor growth,Ki67 expression,caspase-3 positivity,apoptosis rate(TUNEL),and Nrf2/HO-1/NQO1 pathway protein expression levels. Results Oxysophocarpine inhibited BC cell viability,induced apoptosis,and reduced mitochondrial membrane potential in a dose-dependent manner.It significantly suppressed the expression of proliferation-related molecules(Survivin,Ki67),and promoted the expression of apoptosis-related molecules(P21,cleaved caspase-3/9,Bax/Bcl-2 ratio).Additionally,it inhibited Nrf2/HO-1/NQO1 pathway activation and exacerbated oxidative stress(reduced SOD,GSH;increased MDA).Nrf2 overexpression partially reversed these effects of oxysophocarpine.Animal experiments confirmed that oxysophocarpine inhibited tumor growth,reduced proliferation(Ki67),promoted apoptosis(caspase-3,TUNEL),and suppressed Nrf2 pathway activation in vivo. Conclusion Oxysophocarpine effectively inhibits breast cancer cell proliferation,induces apoptosis,and enhances oxidative stress by suppressing the Nrf2/HO-1/NQO1 signaling pathway.

Key words: oxysophocarpine, breast cancer, apoptosis, oxidative stress, Nrf2/HO-1/NQO1 signaling pathway

CLC Number:

R965

CUI Min, ZHANG Tong, SI Mengyuan, LIN Ying, XIE Wenjie, SUN Jirui. Oxysophocarpine Induces Apoptosis of Breast Cancer Cells by Inhibition of Nrf2/HO-1 Signaling Pathway[J]. Journal of Medical Molecular Biology, 2025, 22(6): 571-578.

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