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Anticancer Potential of Ethanolic Extract of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) Dried Fruits on Breast Adenocarcinoma: In Vitro and In Vivo Evidences
Environmental Toxicology ( IF 4.4 ) Pub Date : 2024-10-14 , DOI: 10.1002/tox.24428
Merline Ymele Nguedia, Roland Nhouma Rebe, Berlise Yengwa Bakam, Dieudonné Njamen, Joseph Marie Nkodo Mendimi, Stéphane Zingue

Breast cancer incidence and mortality rate in Cameroonian women is incredibly high, thus there is need for more effective therapy. Xylopia aethiopica dry fruits are traditionally used for both nutritional and medicinal purposes, including the management of diverse ailments such as cancer. This study evaluated the in vitro and in vivo anti‐mammary cancer potential of X. aethiopica. The cytotoxic activity of the ethanolic extract of X. aethiopica dry fruits was assessed at different concentrations against MDA‐MB 231 and MCF‐7 cells using the MTT assay. Additionally, clone formation, apoptosis/necrosis, cell adhesion, cell migration, and chemotaxis were examined. Furthermore, the chemo‐preventive potential of X. aethiopica dry fruit extract (XAE) was evaluated on breast tumors induced by DMBA in 42 female rats of age 45–55 days (~80 g). The normal (NOR) and negative (DMBA) control groups were daily treated with the vehicle, while the positive (Tamox) and test (XAE) groups were administered tamoxifen (3.3 mg/kg) and X. aethiopica extract (75, 150, and 300 mg/kg BW), respectively for 20 weeks. Parameters such as tumor volume and burden, tumor incidence, CA 15‐3 serum level, inflammatory status, antioxidant and histopathology were evaluated. X. aethiopica significantly (p < 0.05) decreased ER+ (MCF‐7) and ER− (MDA‐MB 231) breast adenocarcinoma cell growth from 12.5 to 100 μg/mL after 72 h. At the 100 μg/mL concentration, clone formation, cell proliferation, and migration were notably decreased in MDA‐MB 231 cells after 48 h, while there was an observed rise in cell adhesion to the collagen extracellular matrix. Additionally, there was a rise in apoptotic cell count (p < 0.01) and caspase‐3 activity (p < 0.05) observed in MDA‐MB 231 cells following exposure to XAE at 100 μg/mL. XAE, across all tested doses, demonstrated significant reductions in tumor incidence, burden, and volume, akin to tamoxifen, compared to untreated rats (DMBA). Furthermore, there was an elevation in antioxidants (SOD, CAT, and GSH) and a decrease in pro‐inflammatory cytokines (INF‐γ, TNF‐α, IL‐12, and IL‐6) observed at all tested doses. Overall, X. aethiopica dry fruit displays anticancer potential through caspase‐3‐dependent apoptosis pathways, alongside antioxidant and anti‐inflammatory activities.

中文翻译:


Xylopia aethiopica (Dunal) A. Rich (Annonaceae) 干果乙醇提取物对乳腺癌的抗癌潜力:体外和体内证据



喀麦隆女性的乳腺癌发病率和死亡率高得令人难以置信,因此需要更有效的治疗。Xyobia aethiopica 干果传统上用于营养和药用目的,包括治疗癌症等多种疾病。本研究评估了 X. aethiopica 的体外和体内抗乳腺癌潜力。使用 MTT 测定法评估不同浓度的 X. aethiopica 干果乙醇提取物对 MDA-MB 231 和 MCF-7 细胞的细胞毒活性。此外,还检查了克隆形成、细胞凋亡/坏死、细胞粘附、细胞迁移和趋化性。此外,在 42 只 45-55 天 (~80 g) 的雌性大鼠中评估了 X. aethiopica 干果提取物 (XAE) 对 DMBA 诱导的乳腺肿瘤的化疗预防潜力。正常 (NOR) 和阴性 (DMBA) 对照组每日用载体处理,而阳性 (Tamox) 和测试 (XAE) 组分别给予他莫昔芬 (3.3 mg/kg) 和埃塞俄比亚 X. 提取物 (75、150 和 300 mg/kg BW),持续 20 周。评估肿瘤体积和负荷、肿瘤发生率、CA 15-3 血清水平、炎症状态、抗氧化和组织病理学等参数。X. aethiopica 显着 (p < 0.05) 72 小时后将 ER+ (MCF-7) 和 ER− (MDA-MB 231) 乳腺癌细胞生长从 12.5 μg/mL 降低到 100 μg/mL。在 100 μg/mL 浓度下,48 小时后 MDA-MB 231 细胞的克隆形成、细胞增殖和迁移显着减少,同时观察到细胞与胶原蛋白细胞外基质的粘附增加。此外,凋亡细胞计数 (p < 0.01) 和 caspase-3 活性 (p < 0.05) 在暴露于 100 μg/mL 的 XAE 后的 MDA-MB 231 细胞中观察到。与未治疗的大鼠 (DMBA) 相比,在所有测试剂量中,XAE 显示肿瘤发生率、负荷和体积显着降低,类似于他莫昔芬。此外,在所有测试剂量下观察到抗氧化剂 (SOD、CAT 和 GSH) 升高,促炎细胞因子 (INF-γ、TNF-α、IL-12 和 IL-6) 减少。总体而言,X. aethiopica 干果通过 caspase-3 依赖性细胞凋亡途径以及抗氧化和抗炎活性显示出抗癌潜力。
更新日期:2024-10-14
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