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紫海胆壳的生物学和分子效率体外研究:通过Nrf2/HMOX-1和HIF-1α/VEGF信号通路对T47D乳腺癌细胞系的抗氧化和血管生成作用

Biological and Molecular Efficiency of Paracentrotus lividus Shell in vitro Study: Antioxidant and Angiogenesis Effects Against T47D Breast Cancer Cell Line Via Nrf2/HMOX-1/ and HIF-1α /VEGF Signaling Pathways.

作者信息

Khamis Abeer A, Elkeiy Mai M, El-Gamal Mona M, Saad-Allah Khalil M, Salem Maha M

机构信息

Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.

Zoology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.

出版信息

Cell Biochem Biophys. 2025 Feb 4. doi: 10.1007/s12013-025-01678-6.

Abstract

The sea urchin (Paracentrotus lividus) shell investigation reveals a wealth of bioactive compounds. The bioactive ingredients were observed using UPLCMS/MS profiling. The anti-diabetic, antioxidant, antimicrobial, and anti-inflammatory qualities of P. lividus shell extract were assessed concerning NO, MDA, CAT, and SOD levels. Also, cytotoxic, and anti-angiogenic impact on colon (Caco-2) and breast (T47D) carcinoma cells and quantificated of Nrf2/HMOX-1 and HIF-1α/VEGF pathway expression were evaluated. Our findings indicate that the extract possesses remarkable antioxidant activity with IC equal to (0.1056 ± 0.083 and 30.42 ± 1.52 μg/mL; for DPPH and ABTS respectively), antidiabetic with IC (1.572 ± 0.13 μg/mL) and anti-inflammatory with IC (2.090 ± 0.49 μg/mL). Notably, it exhibits potent anticancer effects against human breast (T47D) and colon (Caco-2) cancer cell lines, (30.55 ± 1.19 and 31.34 ± 1.22 µg/mL respectively). The extract induces oxidative stress and apoptosis, as evidenced by elevated NO and MDA levels, alongside reduced SOD and CAT activities. Moreover, the downregulation of Nrf2/HMOX-1 and HIF-1α/VEGF pathways expression suggests intricate molecular mechanisms underlying its anticancer properties, potentially involving the modulation of oxidative stress and angiogenesis. These findings underscore the sea urchin (P. lividus) shell as a potent reservoir of bioactive constituents with promising applications in pharmaceutical research and offering new avenues for drug discovery.

摘要

对海胆(紫球海胆)壳的研究揭示了大量生物活性化合物。使用超高效液相色谱串联质谱分析对生物活性成分进行了观察。针对一氧化氮(NO)、丙二醛(MDA)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平,评估了紫球海胆壳提取物的抗糖尿病、抗氧化、抗菌和抗炎特性。此外,还评估了其对结肠(Caco - 2)和乳腺(T47D)癌细胞的细胞毒性和抗血管生成作用,并对核因子E2相关因子2/血红素加氧酶-1(Nrf2/HMOX - 1)和缺氧诱导因子-1α/血管内皮生长因子(HIF - 1α/VEGF)通路的表达进行了定量分析。我们的研究结果表明,该提取物具有显著的抗氧化活性,其半数抑制浓度(IC)分别为(0.1056±0.083和30.42±1.52μg/mL;分别针对二苯基苦味酰基自由基(DPPH)和2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸(ABTS)),抗糖尿病活性的IC为(1.572±0.13μg/mL),抗炎活性的IC为(2.090±0.49μg/mL)。值得注意的是,它对人乳腺(T47D)和结肠(Caco - 2)癌细胞系表现出强大的抗癌作用,(分别为30.55±1.19和31.34±1.22μg/mL)。提取物诱导氧化应激和细胞凋亡,这表现为NO和MDA水平升高,同时SOD和CAT活性降低。此外,Nrf2/HMOX - 1和HIF - 1α/VEGF通路表达的下调表明其抗癌特性背后存在复杂的分子机制,可能涉及氧化应激和血管生成的调节。这些发现强调了海胆(紫球海胆)壳是生物活性成分的有力来源,在药物研究中具有广阔的应用前景,并为药物发现提供了新途径。

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