Nguedia Merline Ymele, Rebe Roland Nhouma, Bakam Berlise Yengwa, Njamen Dieudonné, Mendimi Joseph Marie Nkodo, Zingue Stéphane
Faculty of Science, Department of Biological Sciences, University of Maroua, Maroua, Cameroon.
Faculty of Science, Department of Animal Biology and Physiology, University of Yaoundé 1, Yaoundé, Cameroon.
Environ Toxicol. 2025 Feb;40(2):245-263. doi: 10.1002/tox.24428. Epub 2024 Oct 14.
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.
喀麦隆女性乳腺癌的发病率和死亡率极高，因此需要更有效的治疗方法。埃塞俄比亚木瓣树的干果传统上用于营养和药用目的，包括治疗多种疾病，如癌症。本研究评估了埃塞俄比亚木瓣树在体外和体内的抗乳腺癌潜力。使用MTT法评估了埃塞俄比亚木瓣树干果乙醇提取物在不同浓度下对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、凋亡/坏死、细胞黏附、细胞迁移和趋化性。此外，还评估了埃塞俄比亚木瓣树干果提取物（XAE）对42只45-55日龄（约80克）雌性大鼠由二甲基苯并蒽（DMBA）诱导的乳腺肿瘤的化学预防潜力。正常（NOR）和阴性（DMBA）对照组每天用赋形剂处理，而阳性（他莫昔芬）和试验（XAE）组分别给予他莫昔芬（3.3毫克/千克）和埃塞俄比亚木瓣树提取物（75、150和300毫克/千克体重），持续20周。评估了肿瘤体积和负担、肿瘤发生率、CA 15-3血清水平、炎症状态、抗氧化剂和组织病理学等参数。72小时后，埃塞俄比亚木瓣树提取物在12.5至100微克/毫升的浓度下显著（p<0.05）降低了ER+（MCF-7）和ER-（MDA-MB 231）乳腺腺癌细胞的生长。在100微克/毫升的浓度下，48小时后MDA-MB 231细胞中的克隆形成、细胞增殖和迁移显著减少，而观察到细胞与胶原细胞外基质的黏附增加。此外，在100微克/毫升的XAE处理后，MDA-MB 231细胞中的凋亡细胞计数（p<0.01）和半胱天冬酶-3活性（p<0.05）增加。与未处理的大鼠（DMBA）相比，在所有测试剂量下，XAE均显示出肿瘤发生率、负担和体积的显著降低，类似于他莫昔芬。此外，在所有测试剂量下均观察到抗氧化剂（超氧化物歧化酶、过氧化氢酶和谷胱甘肽）升高，促炎细胞因子（干扰素-γ、肿瘤坏死因子-α、白细胞介素-12和白细胞介素-6）降低。总体而言，埃塞俄比亚木瓣树干果通过半胱天冬酶-3依赖性凋亡途径展现出抗癌潜力，同时具有抗氧化和抗炎活性。
