Department of Microbiology, Cellular and Molecular Research Center, Infectious and Tropical Diseases Research Center, Health Research Institute, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Mol Biol Rep. 2023 Jun;50(6):5345-5354. doi: 10.1007/s11033-023-08445-x. Epub 2023 May 8.
Colorectal cancer is one of the widespread and lethal types of malignancies. Recently, antineoplastic attributes of probiotics have attracted lots of attention. Here, we investigated anti-proliferative potential of the non-pathogenic strains Lactobacillus plantarum ATCC 14,917 and Lactobacillus rhamnosus ATCC 7469 on human colorectal adenocarcinoma-originated Caco-2 cells.
Caco-2 and HUVEC control cells were treated with ethyl acetate extracts of the two Lactobacillus strains to assess cell viability by MTT assay. Annexin/PI staining flow cytometry, and caspase-3, -8 and - 9 activity assays were performed to determine the type of cell death induced in extract-treated cells. Expression levels of apoptosis-related genes were evaluated by RT-PCR. Extracts from both L. plantarum and L. rhamnosus specifically targeted the Caco-2 cells and not HUVEC controls, and significantly affected the viability of the colon cancer cell line in a time- and dose-dependent manner. This effect was shown to occur through activation of the intrinsic apoptosis pathway, as indicated by the increased caspase-3 and - 9 activities. While there are limited and conflicting data about the mechanisms underlying the specific antineoplastic attributes of Lactobacillus strains, we clarified the overall induced mechanism. The Lactobacillus extracts specifically down-regulated the expression of the anti-apoptotic bcl-2 and bcl-xl, and simultaneously up-regulated the pro-apoptotic bak, bad, and bax genes in treated Caco-2 cells.
Ethyl acetate extracts of L. plantarum and L. rhamnosus strains could be considered as targeted anti-cancer treatments specifically inducing the intrinsic apoptosis pathway in colorectal tumor cells.
结直肠癌是一种广泛存在且致命的恶性肿瘤类型。最近，益生菌的抗肿瘤特性引起了广泛关注。在这里，我们研究了非致病性菌株植物乳杆菌 ATCC 14917 和鼠李糖乳杆菌 ATCC 7469 对人结直肠腺癌细胞系 Caco-2 的抗增殖潜力。
用两种乳杆菌菌株的乙酸乙酯提取物处理 Caco-2 和 HUVEC 对照细胞，通过 MTT 测定法评估细胞活力。通过 Annexin/PI 染色流式细胞术以及 caspase-3、-8 和 -9 活性测定来确定提取物处理细胞中诱导的细胞死亡类型。通过 RT-PCR 评估凋亡相关基因的表达水平。来自 L. plantarum 和 L. rhamnosus 的提取物特异性靶向 Caco-2 细胞而不是 HUVEC 对照细胞，并以时间和剂量依赖的方式显著影响结肠癌细胞系的活力。这种作用是通过激活内在凋亡途径来实现的，这表明 caspase-3 和 -9 活性增加。虽然关于乳酸菌菌株特定抗肿瘤特性的机制的相关数据有限且存在争议，但我们阐明了总体诱导机制。乳杆菌提取物特异性地下调了抗凋亡 bcl-2 和 bcl-xl 的表达，同时上调了处理后的 Caco-2 细胞中促凋亡 bak、bad 和 bax 基因的表达。
L. plantarum 和 L. rhamnosus 菌株的乙酸乙酯提取物可被视为针对结直肠肿瘤细胞的靶向抗癌治疗方法，可特异性诱导内在凋亡途径。
