Anticancer Potential of Ethanolic Extract of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) Dried Fruits on Breast Adenocarcinoma: In Vitro and In Vivo Evidences.

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Merline Ymele Nguedia,Roland Nhouma Rebe,Berlise Yengwa Bakam,Dieudonné Njamen,Joseph Marie Nkodo Mendimi,Stéphane Zingue
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Abstract

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.
木犀科干果乙醇提取物对乳腺癌的抗癌潜力:体外和体内证据
喀麦隆妇女的乳腺癌发病率和死亡率高得惊人,因此需要更有效的治疗方法。Xylopia aethiopica 干果传统上用于营养和医疗目的,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。采用 MTT 法评估了不同浓度的 X. aethiopica 干果乙醇提取物对 MDA-MB 231 和 MCF-7 细胞的细胞毒性活性。此外,还检测了克隆形成、细胞凋亡/坏死、细胞粘附、细胞迁移和趋化性。此外,还评估了 X. aethiopica 干果提取物(XAE)对 42 只年龄在 45-55 天(约 80 克)的雌性大鼠由 DMBA 诱导的乳腺肿瘤的化学预防潜力。正常对照组(NOR)和阴性对照组(DMBA)每天用药物治疗,而阳性对照组(Tamox)和试验组(XAE)则分别服用他莫昔芬(3.3 毫克/千克)和 X. aethiopica 提取物(75、150 和 300 毫克/千克体重)20 周。对肿瘤体积和负荷、肿瘤发病率、CA 15-3 血清水平、炎症状态、抗氧化性和组织病理学等参数进行了评估。在 100 μg/mL 浓度下,MDA-MB 231 细胞的克隆形成、细胞增殖和迁移在 48 小时后明显降低,同时观察到细胞对胶原细胞外基质的粘附上升。此外,MDA-MB 231 细胞暴露于 100 μg/mL 的 XAE 后,观察到凋亡细胞计数(p < 0.01)和 caspase-3 活性(p < 0.05)上升。与未经处理的大鼠(DMBA)相比,所有测试剂量的 XAE 都能显著降低肿瘤发病率、负荷和体积,与他莫昔芬类似。此外,在所有测试剂量下都观察到抗氧化剂(SOD、CAT 和 GSH)的增加和促炎细胞因子(INF-γ、TNF-α、IL-12 和 IL-6)的减少。总之,X. aethiopica 干果通过依赖于 caspase-3 的细胞凋亡途径显示出抗癌潜力,同时还具有抗氧化和抗炎活性。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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