<p>Dual Targeting of Cell Growth and Phagocytosis by Erianin for Human Colorectal Cancer</p>

Abstract

Objective: To investigate the effect of erianin on tumor growth and immune response in human colorectal cancer cells (CRC). Methods: The effect of erianin on tumor growth was determined by CCK8 and colony formation assay. Western blotting was used to evaluate the expression levels of relevant proteins and qRT-PCR was used to evaluate the mRNA level of the relevant gene. The transcriptional activity of β-catenin was determined by dual-luciferase reporter assay. Cellular thermal shift assay was used to quantify drug-target interactions. The cell surface CD47 was assessed by flow cytometry. The enrichment of H3K27 acetyl marks on CD47 promoter was evaluated by chromatin immunoprecipitation assay. Phagocytosis assay was used to determine the phagocytic activity of macrophage. In vivo role of erianin was studied on xenograft models. Results: We found that erianin significantly decreased cell survival, colony formation, induced cell cycle arrest, and led to cell apoptosis in SW480 and HCT116 cells. Mechanism analysis demonstrated that erianin inhibited the nuclear translocation and transcriptional activity of β-catenin, which might result from erianin-β-catenin interaction. In addition, the downstream gene expressions, such as c-Myc and cyclin D1, was decreased. More interestingly, erianin decreased the expression of CD47 by regulating H3K27 acetyl marks enrichment on CD47 promoter. Consequently, macrophage-mediated phagocytosis was increased. Our in vivo experiments further confirmed the inhibitory effect of erianin on tumor growth. Conclusion: In summary, erianin could inhibit CRC cells growth and promoted phagocytosis, which suggested erianin as a potential therapeutic strategy for CRC patients.

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

“…Erianin at nanomolar level inhibited colony formation in both LNCaP and PC3 cells (Figures 1A, B), which is consistent with previous reports in other cancer types (12,14,17,19,20). However, in contrast to the reported inhibitory effects on cancer cell migration (17,19,20), erianin at 12.5 and 25 nM failed to suppress cell migration in both PCa cell lines (Figures 1C, D).…”

“…Erianin at 20 nM inhibited cell colony formation by 56.5% and 69.6% in LNCaP and PC3 cells, respectively. We also examined whether erianin suppressed PCa cell migration by performing the wound healing assay (Figures 1C, D), following previous erianin studies in other cancer types (17,19,20). However, erianin at 12.5 and 25 nM failed to alter the relative wound density in the scratched areas compared with untreated control during 48 h. Therefore, erianin did not affect PCa cell migration at concentrations sufficient to significantly suppress clonogenicity.…”

“…Erianin induces oxidative stress, leading to apoptosis via the intrinsic apoptosis pathway (14)(15)(16)(17)(18), blocks the cell cycle at the G2/M phase (12,14,17), and has been recently found to trigger ferroptosis, an iron-dependent programmed cell death (19). In addition, treatment of nude mice with erianin significantly inhibit the growth of lung cancer, osteosarcoma, colorectal cancer and bladder cancer xenografts (14,16,17,(19)(20)(21). However, the anti-tumor effects of erianin in PCa have not been examined.…”

Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation

“…Erianin, extracted from rare traditional Chinese medicine Dendrobium chrysotoxum Lindl, was a small-molecule natural compound with a wide range of anticancer potential. Erianin has been reported to inhibit colorectal cancer cells growth by downregulating the transcriptional activity of β-catenin (Sun et al, 2020), induce apoptosis in nasopharyngeal carcinoma by decreasing the phosphorylation of ERK1/2 (Liu et al, 2019), and suppress bladder cancer cell growth through JNK pathways and the mitochondrial apoptosis (Zhu et al, 2004). In our previous study, erianin inhibited the growth and migration via inducing Ca/CaM-dependent ferroptosis and inhibiting cell migration in lung cancer cells (Chen et al, 2020a).…”

The effect and mechanism of erianin on the reversal of oxaliplatin resistance in human colon cancer cells

“…Erianin could inhibit CRC cells growth and promote phagocytosis (Y. Sun et al, 2020), but its role in reversing MDR in CRC is rarely investigated.…”