Tanigawa Kazunari, Tanikawa Takashi, Kitamura Masashi, Hayashi Yasuhiro, Kiriya Mitsuo, Nakamura Yasuhiro, Kawashima Akira, Fujiwara Yoko, Morimoto-Kamata Riyo, Ohkura Naoki, Yui Satoru, Karasawa Ken, Nakamura Ryosuke, Suzuki Koichi
Pharmaceutical Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
School of Pharmacy, Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
Biochem Biophys Rep. 2025 Apr 21;42:102021. doi: 10.1016/j.bbrep.2025.102021. eCollection 2025 Jun.
Spices and herbs, which are derived from natural botanical sources, contain many bioactive compounds and play an important role in human health. The general and specific health benefits of these spices and herbs include anti-inflammatory, antioxidant, and anti-tumorigenic activities. Previously, we showed that cathepsin G, which is a neutrophil-derived serine protease localized in human breast cancer tissues, promotes cancer metastasis via induction of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) expression in MCF-7 human breast cancer cells. Therefore, although regulation of cathepsin G activity is thought to be important in human breast cancer progression, no compounds that inhibit the activity have been identified for therapeutic purposes. In this study, we screened 50 spice and herb extracts. Peppermint, clove, Sichuan pepper, and fenugreek exhibited strong inhibitory effects on cathepsin G activity and suppressed cathepsin G-induced MCF-7 cell aggregation.; importantly, fenugreek suppressed the increase in PAFAH1B2 expression. The IC of 37.38 μg/mL of fenugreek extract that showed inhibitory effect on cathepsin G-induced malignant progression was 5.87 times lower than the concentration that exerted cytotoxic effect. Interestingly, quercetin and trigonelline contained in fenugreek inhibited cathepsin G activity and suppressed the induction of cell aggregation and PAFAH1B2 expression in human breast cancer cells. These results suggest that quercetin and trigonelline are partly responsible for the inhibitory effect of fenugreek on cathepsin G-induced malignant progression of human breast cancer cells. Our findings provide a new breast cancer treatment strategy targeting cathepsin G, and fenugreek may have synergistic effects when combined with therapeutic drugs.
香料和药草源自天然植物来源，含有许多生物活性化合物，对人体健康起着重要作用。这些香料和药草的一般和特定健康益处包括抗炎、抗氧化和抗肿瘤活性。此前，我们发现组织蛋白酶G是一种存在于人类乳腺癌组织中的中性粒细胞衍生的丝氨酸蛋白酶，它通过诱导MCF-7人乳腺癌细胞中血小板活化因子乙酰水解酶1B2（PAFAH1B2）的表达促进癌症转移。因此，尽管组织蛋白酶G活性的调节被认为在人类乳腺癌进展中很重要，但尚未鉴定出用于治疗目的的抑制该活性的化合物。在本研究中，我们筛选了50种香料和药草提取物。薄荷、丁香、花椒和胡芦巴对组织蛋白酶G活性表现出强烈的抑制作用，并抑制了组织蛋白酶G诱导的MCF-7细胞聚集；重要的是，胡芦巴抑制了PAFAH1B2表达的增加。对组织蛋白酶G诱导的恶性进展表现出抑制作用的胡芦巴提取物的IC为37.38μg/mL，比产生细胞毒性作用的浓度低5.87倍。有趣的是，胡芦巴中含有的槲皮素和胡芦巴碱抑制组织蛋白酶G活性，并抑制人乳腺癌细胞中细胞聚集的诱导和PAFAH1B2表达。这些结果表明，槲皮素和胡芦巴碱部分负责胡芦巴对组织蛋白酶G诱导的人乳腺癌细胞恶性进展的抑制作用。我们的研究结果提供了一种针对组织蛋白酶G的新的乳腺癌治疗策略，并且胡芦巴与治疗药物联合使用时可能具有协同作用。
