Journal of ethnopharmacology · 2026
Luteolin, a bioactive compound from Celastrus orbiculatus stem, inhibits cervical cancer via CA2 suppression: A translational study bridging basic research and clinical application.
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Chen Jue, Wu MengKe, Zhang RongRong, Cao Yun, Chen Xiangyan, Liu Xinyu, Liu Yanqing, Jiang Wei, Wang Qiang
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb. is a traditional herb with the effects of eliminating wind and dampness, activating blood circulation and detoxifying.It is commonly used in the treatment of malignant tumors and rheumatoid arthritis in China. Previous basic research has confirmed its significant anti-tumor activity. However, the underlying mechanism of its treatment in cervical cancer has not been reported.
AIM OF THE STUDY: Building on findings from a retrospective clinical analysis, this study applied bioinformatics and experimental validation to elucidate the mechanism by which luteolin, a major constituent of Celastrus orbiculatus stem, and its target protein Carbonic Anhydrase II (CA2) exert inhibitory effects on cervical cancer.
METHODS: A retrospective clinical analysis was first conducted to assess the impact of Celastrus orbiculatus stem (30 g/day) combined with postoperative concurrent chemoradiotherapy (weekly cisplatin) on recurrence in cervical cancer patients. Liquid chromatography-mass spectrometry (LC-MS) was then used to identify the principal active components of Celastrus orbiculatus stem. Public databases were employed to determine the core targets of these active components against cervical cancer. Prognostic analysis was performed using data from The Cancer Genome Atlas (TCGA). Expression of core target proteins was validated in clinical surgical specimens of cervical cancer. Finally, the inhibitory effects of the identified active compound (luteolin) acting through the target protein (CA2) were confirmed using lactate dehydrogenase (LDH) release assays, gene expression modulation, and a murine xenograft tumor model.
RESULTS: Retrospective clinical analysis demonstrated that Celastrus orbiculatus stem (30 g/day) combined with weekly cisplatin concurrent radiotherapy significantly prolonged postoperative disease-free survival in cervical cancer patients. In vitro, the extract of Celastrus orbiculatus stem suppressed cervical cancer cell proliferation. Luteolin was identified as a major constituent of the extract. Further analysis revealed that CA2 was characteristically overexpressed in epithelial tumor cells of cervical cancer tissues, but not in stromal cells, and served as a core target of luteolin. Modulation of CA2 expression or luteolin-mediated intervention effectively inhibited cervical cancer cell proliferation and invasion, promoted apoptosis in vitro, and suppressed the growth of xenograft tumors in vivo.
CONCLUSION: Luteolin is the primary bioactive constituent of Celastrus orbiculatus stem responsible for its inhibitory effects on cervical cancer. CA2, characteristically overexpressed in epithelial-derived cervical cancer cells, plays a pivotal role in promoting cancer cell proliferation and invasion. Luteolin exerts its anticancer activity mainly by targeting and modulating CA2 expression, underscoring CA2 as a potential therapeutic target.
AIM OF THE STUDY: Building on findings from a retrospective clinical analysis, this study applied bioinformatics and experimental validation to elucidate the mechanism by which luteolin, a major constituent of Celastrus orbiculatus stem, and its target protein Carbonic Anhydrase II (CA2) exert inhibitory effects on cervical cancer.
METHODS: A retrospective clinical analysis was first conducted to assess the impact of Celastrus orbiculatus stem (30 g/day) combined with postoperative concurrent chemoradiotherapy (weekly cisplatin) on recurrence in cervical cancer patients. Liquid chromatography-mass spectrometry (LC-MS) was then used to identify the principal active components of Celastrus orbiculatus stem. Public databases were employed to determine the core targets of these active components against cervical cancer. Prognostic analysis was performed using data from The Cancer Genome Atlas (TCGA). Expression of core target proteins was validated in clinical surgical specimens of cervical cancer. Finally, the inhibitory effects of the identified active compound (luteolin) acting through the target protein (CA2) were confirmed using lactate dehydrogenase (LDH) release assays, gene expression modulation, and a murine xenograft tumor model.
RESULTS: Retrospective clinical analysis demonstrated that Celastrus orbiculatus stem (30 g/day) combined with weekly cisplatin concurrent radiotherapy significantly prolonged postoperative disease-free survival in cervical cancer patients. In vitro, the extract of Celastrus orbiculatus stem suppressed cervical cancer cell proliferation. Luteolin was identified as a major constituent of the extract. Further analysis revealed that CA2 was characteristically overexpressed in epithelial tumor cells of cervical cancer tissues, but not in stromal cells, and served as a core target of luteolin. Modulation of CA2 expression or luteolin-mediated intervention effectively inhibited cervical cancer cell proliferation and invasion, promoted apoptosis in vitro, and suppressed the growth of xenograft tumors in vivo.
CONCLUSION: Luteolin is the primary bioactive constituent of Celastrus orbiculatus stem responsible for its inhibitory effects on cervical cancer. CA2, characteristically overexpressed in epithelial-derived cervical cancer cells, plays a pivotal role in promoting cancer cell proliferation and invasion. Luteolin exerts its anticancer activity mainly by targeting and modulating CA2 expression, underscoring CA2 as a potential therapeutic target.