Phenylethanoid Glycosides from <i>Cistanche tubulosa </i>Inhibits the Growth of B16-F10 Cells both <i>in Vitro</i> and <i>in Vivo </i>by Induction of Apoptosis via Mitochondria-dependent Pathway

Abstract

<i>Cistanche tubulosa</i> phenylethanoid glycosides (CTPG) have been shown various biological activities including anti-allergy, hepatoprotective activity and bone regeneration. However, the anti-tumor activity of CTPG needs to be investigated. CTPG was used to treat B16-F10 cells both <i>in vitro</i> and <i>in vivo</i>. We found that CTPG dramatically changed the morphology of B16-F10 cells, and significantly reduced the viability of B16-F10 cells in a dose-dependent and time-dependent manner, which might be mediated by CTPG-induced apoptosis and cell cycle arrest. After CTPG treatment, the expressions of BAX and BCL-2 were up-regulated and down-regulated, respectively. Moreover, mitochondrial membrane potential was reduced and ROS generation was increased. Consequently, the levels of cytochrome c and cleaved-caspase-3 and -9 were up-regulated by CTPG treatment but not for cleaved-caspase-8. We further observed that CTPG significantly inhibited the tumor growth <i>in vivo</i> and improved the survival rate of tumor mice. We also observed that CTPG promoted the proliferation of splenocytes and increased the proportions of CD4⁺ and CD8⁺ T cells in spleens of tumor mice. The results showed that CTPG induced the apoptosis of B16-F10 cells through mitochondria-dependent pathway, suggesting that CTPG could be a potential candidate for treatment of cancer.