Protosappanin B Exerts Anti-tumor Effects on Colon Cancer Cells via Inhibiting GOLPH3 Expression

Abstract

Protosappanin B (PSB) is a key active component of Lignum Sappan extract. Although the antiproliferative effects of Lignum Sappan extract have been demonstrated in various cancer cells, relatively little is known about the effects of PSB on tumor progression. The aim of this study was to explore the anti-tumor effects of PSB on human colon cancer cells by regulation of intracellular signaling pathways and Golgi phosphoprotein 3 (GOLPH3) expression in vitro and in vivo. Our results showed that PSB effectively inhibited the viability and migration of SW620 cells and induced apoptosis, but had poor effect on HCT116 cells. Furthermore, PSB significantly reduced the expression of p-AKT, p-p70S6K, β-catenin, and p-ERK1/2 proteins in SW620 cells, and this effect was reversed by the corresponding signaling pathway agonists. Interestingly, PSB could also suppress GOLPH3 expression of SW620 cells in a concentration-dependent manner, but SW620 cells transfected with lentiviral vectors overexpressing GOLPH3 can effectively resist the cytotoxic activity of PSB in vitro. The xenograft experiment of SW620 cells with LV-GOLPH3 confirmed that PSB distinctly inhibited the tumor growth via suppressing GOLPH3 expression. Collectively, these findings clarified a new anti-cancer mechanism of PSB through inhibition of GOLPH3 expression and intracellular signaling pathways in colon cancer cells. PSB may be a potential new drug for colon cancer.

Protosappanin B enhances the chemosensitivity of 5-fluorouracil in colon adenocarcinoma by regulating the LINC00612/microRNA-590-3p/Golgi phosphoprotein 3 axis

“…In recent years, its anti-tumor properties have also been discovered. For instance, PSB can inhibit the proliferation of human bladder cancer cell lines and colon cancer cell lines [ 19 ]. To be specific, PSB inhibits the proliferation and promotes the apoptosis of human bladder cancer cells via interference with cell cycle regulation [ 20 ].…”

“…To verify the successful establishment of resistant cells, SW620 and LOVO cells were treated with 5-FU (0, 4, 8, 16, 32, and 64 μM; Nanjing Chia-Tai Tianqing Pharmaceutical Company) along with resistant cells to establish cell viability [ 19 ]. Appropriate concentrations of PSB were screened for subsequent experiments by treating 5-FU SW620 and 5-FU LOVO cells with different concentrations of PSB (Shanghai Yuanye Bio-Technology Company) to measure cell viability.…”

“…Intraperitoneal injection of 30 mg/kg 5-FU [ 20 ] was performed every 3 days from the 6th day, for 8 cycles. From day 7 onwards, 20 mg/kg PSB [ 19 ] was injected intraperitoneally every three days for eight cycles. Graft size was measured and recorded with Vernier calipers every other week.…”

“…Growing evidence has demonstrated that natural products can modulate lncRNAs to participate in the regulation of chemoresistance of tumors [ 16 – 18 ]. Protosappanin B (PSB), a Caesalpinia sappan Linn extract, has been investigated and could suppress various tumor processes [ 19 – 21 ]. However, whether PSB alleviates chemoresistance of colon adenocarcinoma remains unclear.…”

Golgi phosphoprotein 3 induces autophagy and epithelial–mesenchymal transition to promote metastasis in colon cancer

“…When Golgi apparatus stress is ameliorated, GOLPH3 expression decreases, and the phosphorylation of the PI3K/Akt/mTOR pathway is promoted [ 62 ]. Previous studies that found GOLPH3 promotes Akt in colon cancer were performed using the cell lines HCT-116 [ 40 ], LoVo [ 58 ], and SW620 [ 63 ]. To the best of our knowledge, no study has constructed and used GOLPH3-overexpressing and -silenced cell lines to investigate the impact of GOLPH3 on Akt in HCT-116 and HT-29 cells.…”