Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway

Abstract

Malignant melanoma, one of the most aggressive skin cancers, has a very high mortality rate. Currently, the number of drugs to treat melanoma is low. Although new immunotherapeutic approaches based on the use of antibodies against immune checkpoints have shown long term responses, it is urgent to develop novel anti-melanoma drugs with a high efficiency and a low toxicity in a large number of patients. Lycorine, a natural product, has been reported to exert antitumor effects on some cancers. However, the impact of lycorine on melanoma cells is still unknown. Using the CCK8 assay, we found that lycorine can suppress the proliferation of melanoma A375 cells in a dose-time-dependent manner. Moreover, a transwell assay showed that lycorine inhibited the migration and invasion of A375 cells significantly. Further, lycorine treatment could induce the apoptosis of the A375 cells. Biochemical analyses showed that the expression level of the anti-apoptosis Bcl-2 protein decreased, while the expression of the pro-apoptosis protein Bax and active caspase-3 increased after lycorine treatment. Finally, using western blot assay, we found that the antitumor effects of lycorine on A375 cells might be through the inactivation of the PI3K/Akt signaling pathway. Based on these observations, we suggest that lycorine may be an interesting candidate for further studies on its ability to represent a novel antitumor drug for human melanoma treatment in the future.

Metabolomic comparison between natural Huaier and artificial cultured Huaier

“…Dicentrine can enhance the apoptosis and inhibit the invasion of A549 lung adenocarcinoma cells induced by TNF‐ α (Ooppachai et al, 2019). Lycorine has good antitumor activity and can inhibit the growth of human osteosarcoma cells, melanoma A375 cells, HepG2 hepatoblastoma cells and non‐small cell lung cancer in many ways (Jiang & Liu, 2018; Li, Zhang, et al, 2019; Liu, Tang, et al, 2019; Yuan et al, 2020). Camptothecin is a broad‐spectrum antineoplastic drug, and its analogues are used in the treatment of colon, ovarian and small cell lung cancer (Ghanbari‐Movahed et al, 2021).…”

Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways

“…Furthermore, pristimerin reduced migration and invasion by the regulation of pAKT and pFoxO3a expression with confirming the knock-down of AKT in UM-1 cells [ 61 ]. In human A375 and mouse B16F10 melanoma cells, bioactive compounds such as gambogic acid [ 62 ], melittin [ 63 ], kaempferol [ 64 ], euplotin C [ 65 ], lycorine [ 66 ], oxyfadichalcone C [ 67 ], isoliquiritigenin [ 68 ], muniziqi granule/harmine [ 69 ], apigenin [ 70 ] and casticin [ 71 ] inhibited cell proliferation, colony formation, migration and invasion by downregulating the expression of pPI3K, pAKT, pmTOR and pGSK3 β together with the expression of related biomarkers including p27, cyclin D1, LC3, 4EBP1, Bax, Bcl-2 and MMPs. A375.S2 cells, which are investigated in studies involving metastasis, chrysin [ 72 ] and berberine [ 73 ], significantly reduced cell mobility, migration and invasion by decreasing the level of MMPs, N-cadherin and uPA expression through the inhibition of PKC and pAKT.…”

Effect of lycorine on the structure and function of hepatoma cell membrane in vitro and in vivo

“…In recent years, the antitumor effect of lycorine has become a hot topic. Studies have reported that lycorine has significant inhibitory effects on different kinds of cancer cells [4][5][6][7][8][9][10][11]. Therefore, lycorine has a high research value as a potential antitumor drug.…”