The Inhibitory Effect And Mechanism Of The Chinese Herbal Medicinal Monomers Lycorine And Jatrorrhizine On Melanoma Cell-dominant Neovascularization

Melanoma is a malignant tumor which seriously harms human health, and its incidence andmorbidity have soared in recent years; however, the pathogenesis of malignant melanoma is stillenigmatic, the effective anti-melanoma drugs are lack, and the efficacy of existing Chineseherbal medicine for melanoma therapy is low; hence, more effective anti-cancer drugs remainto be explored. In this investigation, utilizing the tumor cells as a model, we first screened andselected two anti-melanoma traditional Chinese medicinal herbs, Lycoris and Goldthread, from120medicinal herbs, and then profoundly studied the anti-melanoma vasculogenic effect of twomonomers lycorine hydrochloride (LH) from Lycoris and Jatrorrhizine hydrochloride (JH) fromGoldthread. The results showed that both of the monomers effectually inhibited the melanomaC8161cell-dominant vasculogenesis. The first monomer LH inhibited C8161cell proliferationin vitro with IC50of0.99μM and potently suppressed C8161-mediated formation ofcapillary-like structures in vitro and neovascularization in vivo. The mechanism study indicatedthat LH inhibited expression of a key vasculogenic gene VE-cadherin; the chemiluminescenceassay showed that LH effectively impeded the promoter activity of VE-cadherin gene. Inaddition, LH hindered C8161cell proliferation and resulted in cell cycle arrest at G0/G1phase by up-regulation of expression of p21gene, but it did not affect C8161cell apoptosis.Besides, we also studied the anti-melanoma effect of another monomer JH and found that itretarded C8161cell proliferation in vitro with IC50of47.35μM and curbed the formation ofcapillary-like structures in vitro and C8161cell-dominant vasculogenesis in vivo, which wereassociated with the down regulation of VE-cadherin expression. Similar to LH, JH also inducedC8161cell cycle arrest at G0/G1phase and had no obvious effect on cell apoptosis. Inconclusion, LH and JH effectively inhibit melanoma C8161cell-dominantneovascularization through suppression of VE-cadherin gene expression; and the twomonomers also diminish melanoma growth and suppress cell proliferation. Since theanti-tumor neovascularization effect of LH and JH has not been reported yet, this studyprovided new information for anti-melanoma neovasculorization and found a new cut-in point for anti-melanoma drug discovery from the traditional Chinese medicinal herbs inthe future.