Jo Hyun Woo, Kim Moon-Moo
Department of Applied Chemistry, Dong-Eui University, Busan, Republic of Korea.
Department of Food Science and Technology, Dong-Eui University, Busan, Republic of Korea.
J Food Biochem. 2022 Dec;46(12):e14468. doi: 10.1111/jfbc.14468. Epub 2022 Oct 3.
When cancer cells transform into malignant tumors, they gain the ability to ignore growth-inhibiting signals, have endless reproduction potential, resist apoptosis, and induce angiogenesis and invade other tissues. Matrix metalloproteinases (MMPs) allow tumor cells to move into surrounding tissues in many malignancies, but metastasis is blocked by MMPs inhibitors. Therefore, the effect of β-caryophyllene oxide (CPO) contained in Piper nigrum on Mitogen-activated protein kinase (MAPKs) related to MMPs signaling pathways in human fibrosarcoma was examined in HT1080 cells. The effect of CPO on cell viability was performed using the MTT assay. Cytotoxicity was observed in the presence of CPO above 16 μM. Next, gelatin zymography was performed in the cells activated with phorbol-12-myristate-13-acetate (PMA). It was found that CPO at 32 μM reduced MMP-9 activity by 28% and MMP-2 activity by 60%. To confirm the effect of CPO on MMPs, Western blot analyses for MMP-2, MAPKs were carried out in this study. The expression level of MMP-2 was reduced by 45% in the presence of CPO at 32 μM, but those of p-p38 and p-ERK were reduced by 50% and 40%, respectively. CPO decreased the expression levels of MMP-2 and MMP-9 in the immunofluorescence staining assay. Finally, an invasion assay was performed in PMA-treated human fibrosarcoma cells. It was demonstrated that CPO reduced cell invasion of HT1080 cells in a dose-dependent manner starting at a concentration of 2 μM. The above results suggest that CPO could be used as a potential candidate for the treatment of metastasis by inhibiting MMP-2, p-p38 and p-ERK. PRACTICAL APPLICATIONS: Cancer makes it easier for cells to spread to other tissue via blood and lymph systems. Tumor cells deplete nutrients and induce angiogenesis, which penetrates and spreads to other parts of the body. As a result, the effect of CPO against cell invasion was evaluated in this study. CPO reduced cancer cell invasion by inactivating p-ERK and p-p38, according to the findings. MMP-2 and MMP-9 activation and protein expression were also decreased by CPO. As a result, CPO might be used as an alternate treatment agent for preventing metastasis.
当癌细胞转变为恶性肿瘤时，它们获得了忽略生长抑制信号的能力，具备无限增殖潜能，抵抗细胞凋亡，并诱导血管生成以及侵袭其他组织。基质金属蛋白酶（MMPs）使肿瘤细胞在许多恶性肿瘤中能够侵入周围组织，但MMPs抑制剂可阻断转移。因此，在HT1080细胞中检测了黑胡椒中含有的β-石竹烯氧化物（CPO）对与MMPs信号通路相关的丝裂原活化蛋白激酶（MAPKs）的影响。使用MTT法检测CPO对细胞活力的影响。在CPO浓度高于16μM时观察到细胞毒性。接下来，在用佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）激活的细胞中进行明胶酶谱分析。发现32μM的CPO使MMP-9活性降低28%，MMP-2活性降低60%。为了证实CPO对MMPs的作用，本研究对MMP-2、MAPKs进行了蛋白质印迹分析。在32μM的CPO存在下，MMP-2的表达水平降低了45%，但p-p38和p-ERK的表达水平分别降低了50%和40%。在免疫荧光染色试验中，CPO降低了MMP-2和MMP-9的表达水平。最后，在PMA处理的人纤维肉瘤细胞中进行侵袭试验。结果表明，从2μM的浓度开始，CPO以剂量依赖的方式降低了HT1080细胞的侵袭。上述结果表明，CPO可作为通过抑制MMP-2、p-p38和p-ERK治疗转移的潜在候选物。实际应用：癌症使细胞更容易通过血液和淋巴系统扩散到其他组织。肿瘤细胞消耗营养并诱导血管生成，血管生成会渗透并扩散到身体的其他部位。因此，本研究评估了CPO对细胞侵袭的作用。根据研究结果，CPO通过使p-ERK和p-p38失活来降低癌细胞侵袭。CPO还降低了MMP-2和MMP-9的激活及蛋白表达。因此，CPO可能用作预防转移的替代治疗药物。
