Coptisine from Rhizoma Coptidis Suppresses HCT-116 Cells-related Tumor Growth in vitro and in vivo

Abstract

Colorectal cancer is one of the most common causes of cancer-related death in humans. Coptisine (COP) is a natural alkaloid from Coptidis Rhizoma with unclear antitumor mechanism. Human colon cancer cells (HCT-116) and xenograft mice were used to systematically explore the anti-tumor activity of COP in this study. The results indicated that COP exhibited remarkably cytotoxic activities against the HCT-116 cells by inducing G1-phase cell cycle arrest and increasing apoptosis, and preferentially inhibited the survival pathway and induced the activation of caspase proteases family of HCT-116 cells. Experimental results on male BALB/c nude mice confirmed that orally administration of COP at high-dose (150 mg/kg) could suppress tumor growth, and may reduce cancer metastasis risk by inhibiting the RAS-ERK pathway in vivo. Taken together, the results suggested that COP may be potential as a novel anti-tumor candidate in the HCT-116 cells-related colon cancer, further studies are still needed to suggest COP for the further use.

Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects

“…Coptisine, another alkaloid of Coptidis rhizoma is proved to have anticancer effects when used in concentrations of 150 mg/kg against BALB/c nude mice by suppressing tumor growth and reducing cancer metastasis. The inhibition of the RAS-ERK pathway was suggested as the mechanism for this activity [160]. Another study was also performed on the nude mice on the HepG2 cells by applying the aqueous extract of H. diffusa which inhibits proliferation of cells in a dose-dependent manner, also delay S phase and arrest cells in G 0 /G 1 phase [161].…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…174 The PI3K-Akt and mitogen-activated protein kinase (MAPK) signaling pathways in the treatment of thyroid carcinoma also were affected. 175,176 A related isoquinoline alkaloid, coptisine (165), also affected PI3K/Akt and mitochondrial-associated apoptotic pathways, 177 and exhibited remarkable cytotoxic activities against HCT-116 cells by activating the caspase protease family, inducing G1-phase cell cycle arrest and increasing apoptosis. 178 The protoberberine alkaloid palmatine (166) induced cell apoptosis in MCF-7 breast cancer cells; after the treatment (1 μM, 10.8 J/cm 2 ), the early apoptotic and late apoptotic rates increased significantly up to 21.16% and 9.86% in photodynamic therapy.…”

Coptisine-induced inhibition ofHelicobacter pylori: elucidation of specific mechanisms by probing urease active site and its maturation process

“…Coptisine (structure shown in Figure 1 ), an active protoberberine alkaloid present in Rhizoma Coptidis, has the same isoquinoline parent structure as alkaloids (berberine, palmatine, epiberberine, and jatrorrhizine) but differs in the appended groups (namely with two methylenedioxy groups). Coptisine exhibits anti-enzyme 38 , antimicrobial 35 , anti-tumour 39 , and gastroprotective effects 40 . However, comparisons of coptisine with other four alkaloids in their biological activities are rarely explored.…”