Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon.
Department of Morphological Sciences and Pathological Anatomy, Faculty of Medicine and Biomedical Sciences, University of Garoua, Garoua, Cameroon.
Environ Toxicol. 2023 Sep;38(9):2069-2083. doi: 10.1002/tox.23830. Epub 2023 Jun 13.
Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins β-1 and β-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 μg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin β-1 and β-4 was increased in presence of 100 μg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.
尽管现代医学取得了巨大进展，但前列腺癌（PCa）仍然是一个重大的公共卫生问题，因为它的发病率和死亡率都很高。尽管研究表明，来自黄瓜的葫芦素在体外具有抗肿瘤作用，但整个种子油的抗癌作用尚未得到证实。本研究评估了黄瓜（CS）籽油的体外抗癌机制及其对苯并（a）芘（BaP）诱导的 Wistar 大鼠前列腺癌的可能化学预防潜力。评估了细胞生长、克隆形成、细胞死亡机制、细胞黏附和迁移以及整合素β-1和β-4的表达。在体内诱导 56 只雄性大鼠发生 PCa，相对于 8 只正常对照大鼠，随机分为正常（NOR）和阴性（BaP）对照组，给予蒸馏水；阳性对照组（Caso）用卡巴他赛（13.5mg/kg BW）治疗。一组给予 500mg/kg BW 的全种子提取物；而其余三组分别用 42.5、85 和 170mg/kg BW 的 CS 籽油治疗。终点为：形态学（前列腺肿瘤重量和体积）、生化（总蛋白、前列腺特异性抗原（PSA）、氧化应激标志物如 MDA、GSH、过氧化氢酶和 SOD）和组织学。结果表明，CS 籽油可显著且浓度依赖性地降低 DU145 前列腺癌细胞的生长和克隆形成（最佳浓度=100μg/mL）。它略微增加了凋亡细胞的数量，抑制了 DU145 细胞的迁移和侵袭，同时降低了它们对固定化胶原蛋白和纤维蛋白原的黏附。在存在 100μg/mL CS 油的情况下，整合素β-1和β-4的表达增加。在体内，BaP 显著增加了 PC 肿瘤（75%）的发生率、总蛋白和 PSA 水平、促炎细胞因子（TNF-α、IL-1 和 IL-6）和 MDA 水平，与 NOR 相比。CS 籽油通过显著降低 PC 发生率（12.5%），增加血清中抗氧化剂（SOD、GSH 和过氧化氢酶）和抗炎细胞因子 IL-10 的水平，显著对抗 BaP 的作用。在 BaP 组中，PCa 腺癌是最具代表性的肿瘤，而用 85 和 170mg/kg 治疗的大鼠则阻止了它，就像用卡巴他赛一样。研究表明，CS 可能在体外和体内提供肿瘤抑制作用，使其成为支持当前治疗方案的一个有趣候选者。
