Department of Drug Development, College of Medicine, Inha University, Sinheung‑dong, Jung-gu, Incheon 400-712, Republic of Korea.
Oncol Rep. 2013 Aug;30(2):801-8. doi: 10.3892/or.2013.2517. Epub 2013 Jun 4.
Pulsatilla koreana has been used as a traditional medicine for the treatment of various diseases. The purpose of this study was to determine whether SB365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana inhibits the progression of pancreatic cancer. We found that SB365 strongly suppressed the growth and proliferation of 5 human pancreatic cancer cell lines (MIAPaCa-2, BXPC-3, PANC-1, AsPC-1 and HPAC). The apoptotic effect of SB365 was demonstrated by increased levels of cleaved caspase-3 and decreased Bcl-2 expression via mitochondrial membrane potential, as well as elevated numbers of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells. SB365 was also found to exert an anti-angiogenic effect by decreasing the expression of HIF-1α and VEGF, major factors of angiogenesis, which was confirmed by the suppression of tumor sphere formation of pancreatic cancer cells. An in vivo mouse xenograft study showed that SB365 significantly inhibited tumor growth through the induction of apoptosis and inhibition of angiogenesis with strong anticancer activity. Therefore, SB365 is a good candidate as a natural product for use in the treatment of pancreatic cancer.
白头翁已被用作治疗各种疾病的传统药物。本研究旨在确定从白头翁根部分离得到的白头翁皂甙 D（SB365）是否抑制胰腺癌的进展。我们发现 SB365 强烈抑制了 5 个人胰腺癌细胞系（MIAPaCa-2、BXPC-3、PANC-1、AsPC-1 和 HPAC）的生长和增殖。通过线粒体膜电位增加 cleaved caspase-3 的水平和降低 Bcl-2 表达，以及增加末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）阳性凋亡细胞的数量，证明了 SB365 的促凋亡作用。SB365 还通过降低血管生成的主要因素 HIF-1α 和 VEGF 的表达发挥抗血管生成作用，这通过抑制胰腺癌细胞的肿瘤球形成得到证实。体内小鼠异种移植研究表明，SB365 通过诱导细胞凋亡和抑制血管生成来显著抑制肿瘤生长，具有很强的抗癌活性。因此，SB365 是一种很有前途的天然产物，可用于治疗胰腺癌。
