Department of Laboratory Medicine, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, China.
Department of Acupuncture and Moxibustion, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, China.
Oncol Res. 2024 Nov 13;32(12):1881-1890. doi: 10.32604/or.2024.048007. eCollection 2024.
Caffeic acid (CA) is considered a promising phytochemical that has inhibited numerous cancer cell proliferation. Therefore, it is gaining increasing attention due to its safe and pharmacological applications. In this study, we investigated the role of CA in inhibiting the Interleukin-6 (IL-6)/Janus kinase (JAK)/Signal transducer and activator of transcription-3 (STAT-3) mediated suppression of the proliferation signaling in human prostate cancer cells.
The role of CA in proliferation and colony formation abilities was studied using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and colony formation assays. Tumour cell death and cell cycle arrest were identified using flow cytometry techniques. CA treatment-associated protein expression of mitogen-activated protein kinase (MAPK) families, IL-6/JAK/STAT-3, proliferation, and apoptosis protein expressions in PC-3 and LNCaP cell lines were measured using Western blot investigation.
We have obtained that treatment with CA inhibits prostate cancer cells (PC-3 and LNCaP) proliferation and induces reactive oxygen species (ROS), cell cycle arrest, and apoptosis cell death in a concentration-dependent manner. Moreover, CA treatment alleviates the expression phosphorylated form of MAPK families, i.e., extracellular signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinase (JNK), and p38 in PC-3 cells. IL-6 mediated JAK/STAT3 expressions regulate the proliferation and antiapoptosis that leads to prostate cancer metastasis and migration. Therefore, to mitigate the expression of IL-6/JAK/STAT-3 is considered an important target for the treatment of prostate cancer. In this study, we have observed that CA inhibits the expression of IL-6, JAK1, and phosphorylated STAT-3 in both PC-3 and LNCaP cells. Due to the inhibitory effect of IL-6/JAK/STAT-3, it resulted in decreased expression of cyclin-D1, cyclin-D2, and CDK1 in both PC-3 cells. In addition, CA induces apoptosis by enhancing the expression of Bax and caspase-3; and decreased expression of Bcl-2 in prostate cancer cells.
Thus, CA might act as a therapeutical application against prostate cancer by targeting the IL-6/JAK/STAT3 signaling axis.
咖啡酸（CA）被认为是一种很有前途的植物化学物质，能抑制多种癌细胞的增殖。因此，由于其安全和药理学应用，它正受到越来越多的关注。在这项研究中，我们研究了 CA 在抑制白细胞介素 6（IL-6）/Janus 激酶（JAK）/信号转导和转录激活因子 3（STAT-3）介导的人前列腺癌细胞增殖信号抑制中的作用。
使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）测定法和集落形成测定法研究 CA 对增殖和集落形成能力的作用。通过流式细胞术技术鉴定肿瘤细胞死亡和细胞周期阻滞。使用 Western blot 研究测定 CA 处理相关的丝裂原活化蛋白激酶（MAPK）家族、IL-6/JAK/STAT-3、增殖和凋亡蛋白在 PC-3 和 LNCaP 细胞系中的表达。
我们发现，CA 抑制前列腺癌细胞（PC-3 和 LNCaP）增殖，并以浓度依赖的方式诱导活性氧（ROS）、细胞周期阻滞和凋亡细胞死亡。此外，CA 处理减轻了 MAPK 家族中磷酸化形式的表达，即 PC-3 细胞中的细胞外信号调节激酶 1（ERK1）、c-Jun N-末端激酶（JNK）和 p38。白细胞介素 6 介导的 JAK/STAT3 表达调节增殖和抗凋亡，导致前列腺癌转移和迁移。因此，减轻 IL-6/JAK/STAT-3 的表达被认为是治疗前列腺癌的一个重要靶点。在这项研究中，我们观察到 CA 抑制了 PC-3 和 LNCaP 细胞中 IL-6、JAK1 和磷酸化 STAT-3 的表达。由于 IL-6/JAK/STAT-3 的抑制作用，导致 PC-3 细胞中环素-D1、环素-D2 和 CDK1 的表达降低。此外，CA 通过增强 Bax 和 caspase-3 的表达和降低前列腺癌细胞中 Bcl-2 的表达诱导细胞凋亡。
因此，CA 通过靶向 IL-6/JAK/STAT3 信号轴，可能作为一种治疗前列腺癌的治疗应用。
