Park Kyung-Ran, Leem Hyun Hee, Lee Joonyeop, Kwon Il Keun, Hong Jin Tae, Yun Hyung-Mun
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University Seoul 02453, South Korea.
Biomedical Science Institute, School of Medicine, Kyung Hee University Seoul 02447, South Korea.
Am J Cancer Res. 2021 Sep 15;11(9):4541-4550. eCollection 2021.
Natural compounds have emerged as an approach in cancer therapy. Nakai is used as a traditional medicinal plant that found throughout China and Korea. However, anti-cancer effects of Hederoside C (HedC) isolated from has not been investigated in osteosarcoma. The present study aimed to demonstrate anti-cancer functions of HedC against human osteosarcoma cells. Herein, we found that HedC suppressed the proliferation of MG63 cells and U2OS cells in the dose- and time-dependent manner, and caused intrinsic apoptosis pathways as evidenced by morphological changes, TUNEL-positive cells, cleaved-PARP, and cleaved-caspase 9 and 3. HedC increased p53, Bax, and p21, whereas HedC reduced Bcl-2. HedC-mediated apoptosis was accompanied by decreases in the mitogen-activated protein kinases (MAPKs) and STAT3 phosphorylation. Wound healing and Boyden chamber assays also showed the anti-metastatic effects of HedC by suppressing migration and invasion. In addition, the anti-cancer effects of HedC were observed in xenograft mice model, and HedC treatment induced the decreased PCNA and p-STAT3 as well as the increased p53 and cleaved caspase-3. Taken together, our results provide evidence that HedC might be an attractive therapeutic strategy against osteosarcoma.
天然化合物已成为癌症治疗的一种方法。中井用作一种在中国和韩国均有发现的传统药用植物。然而，从该植物中分离出的常春藤皂苷元C（HedC）对骨肉瘤的抗癌作用尚未得到研究。本研究旨在证明HedC对人骨肉瘤细胞的抗癌功能。在此，我们发现HedC以剂量和时间依赖性方式抑制MG63细胞和U2OS细胞的增殖，并通过形态学变化、TUNEL阳性细胞、裂解的PARP以及裂解的半胱天冬酶9和3证明其引发了内源性凋亡途径。HedC增加了p53、Bax和p21，而降低了Bcl-2。HedC介导的凋亡伴随着丝裂原活化蛋白激酶（MAPKs）和STAT3磷酸化的减少。伤口愈合和博伊登室试验也显示HedC通过抑制迁移和侵袭具有抗转移作用。此外，在异种移植小鼠模型中观察到了HedC的抗癌作用，HedC治疗导致增殖细胞核抗原（PCNA）和磷酸化STAT3减少，以及p53和裂解的半胱天冬酶-3增加。综上所述，我们的结果提供了证据表明HedC可能是一种有吸引力的抗骨肉瘤治疗策略。
