菠萝醋在体外和体内对小鼠乳腺细胞的凋亡及转移抑制潜力
Apoptosis and metastasis inhibitory potential of pineapple vinegar against mouse mammary gland cells in vitro and in vivo.
作者信息
Mohamad Nurul Elyani, Abu Nadiah, Yeap Swee Keong, Lim Kian Lam, Romli Muhammad Firdaus, Sharifuddin Shaiful Adzni, Long Kamariah, Alitheen Noorjahan Banu
机构信息
1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor Malaysia.
2UKM Molecular Biology Institute (UMBI), UKM Medical Centre, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur Malaysia.
出版信息
Nutr Metab (Lond). 2019 Jul 26;16:49. doi: 10.1186/s12986-019-0380-5. eCollection 2019.
BACKGROUND
Plant-based food medicine and functional foods have been consumed extensively due to their bioactive substances and health-beneficial effects. Vinegar is one of them due to its bioactivities, which confers benefits on human body. Our previous study has produced pineapple vinegar that is rich in gallic acid and caffeic acid via 2 steps fermentation. There are many evidences that show the effectiveness of these resources in inhibiting the proliferation and metastasis of the cancer cells through several mechanisms.
METHODS
Freeze-dried pineapple vinegar was evaluated for its in vitro apoptosis and metastasis inhibitory potential using MTT, cell cycle, Annexin V and scratch assays. The in vivo test using BALB/c mice challenged with 4 T1 cells was further investigated by pre-treating the mice with 0.08 or 2 ml/kg body weight of freshly-prepared pineapple vinegar for 28 days. The tumor weight, apoptotic state of cells in tumor, metastasis and immune response of the untreated and pineapple vinegar treatment group were evaluated and compared.
RESULTS
From the in vitro study, an IC value of 0.25 mg/mL after 48 h of treatment was established. Annexin V/PI and scratch closure assays showed that pineapple vinegar induced 70% of cell population to undergo apoptosis and inhibited 30% of wound closure of 4 T1 cells. High concentration of pineapple vinegar (2 ml/kg body weight) led to the reduction of tumor weight and volume by 45%as compared to the untreated 4 T1-challenged mice. This effect might have been contributed by the increase of T cell and NK cells population associated with the overexpression of IL-2 andIFN-γ cytokines and splenocyte cytotoxicity. Furthermore, fewer instances of metastasis events were recorded in the pineapple vinegar treatment group and this could be explained by the downregulation of inflammation related genes (iNOS, NF-kB and COX2), metastasis related genes (iCAM, VEGF and MMP9) and angeogenesis related genes (CD26, TIMP1, HGF, MMP3, IGFBP-1 and IGFBP-2).
CONCLUSION
The ability of pineapple vinegar to delay cancer progression portrayed its potential as chemopreventive dietry intervention for cancer therapy.
背景
植物性食品药物和功能性食品因其生物活性物质和对健康有益的作用而被广泛食用。醋因其生物活性而成为其中之一，对人体有益。我们之前的研究通过两步发酵生产出了富含没食子酸和咖啡酸的菠萝醋。有许多证据表明，这些物质通过多种机制在抑制癌细胞增殖和转移方面具有有效性。
方法
使用MTT、细胞周期、膜联蛋白V和划痕试验评估冻干菠萝醋的体外凋亡和转移抑制潜力。通过用0.08或2毫升/千克体重的新鲜制备的菠萝醋预处理BALB/c小鼠28天，进一步研究用4T1细胞攻击的BALB/c小鼠的体内试验。评估并比较未处理组和菠萝醋处理组的肿瘤重量、肿瘤细胞的凋亡状态、转移和免疫反应。
结果
体外研究表明，处理48小时后的IC值为0.25毫克/毫升。膜联蛋白V/碘化丙啶和划痕闭合试验表明，菠萝醋诱导70%的细胞群体发生凋亡，并抑制4T1细胞30%的伤口闭合。与未处理的4T1攻击小鼠相比，高浓度的菠萝醋（2毫升/千克体重）使肿瘤重量和体积减少了45%。这种效果可能是由于T细胞和NK细胞群体的增加，以及IL-2和IFN-γ细胞因子的过度表达和脾细胞细胞毒性。此外，菠萝醋处理组记录到的转移事件较少，这可以通过炎症相关基因（iNOS、NF-κB和COX2）、转移相关基因（iCAM、VEGF和MMP9）和血管生成相关基因（CD26、TIMP1、HGF、MMP3、IGFBP-1和IGFBP-2）的下调来解释。
结论
菠萝醋延缓癌症进展的能力表明其作为癌症治疗化学预防饮食干预的潜力。
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