Supercritical Extract of Cannabis sativa Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest

Abstract

Colorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. Cannabis sativa Linne (C. sativa) is a popular medicinal plant used by humans to treat many diseases. Recently, extracts of C. sativa have shown diverse pharmacological effects as a result of choosing different extraction methods. In this study, we performed experiments to confirm the inhibitory effect and related mechanisms of supercritical extract of C. sativa on metastatic CRC cells. The effect of SEC on the viability of CRC cell lines, CT26 and HCT116, was determined using CCK reagent. Flow cytometry was performed to confirm whether SEC can promote cell cycle arrest and apoptosis. Additionally, SEC reduced proliferation of CT26 and HCT116 cells without causing toxicity to normal colon cell line CCD-18Co cells. SEC treatment reduced colony formation in both CRC cell lines, promoted G0/G1 phase arrest and apoptosis in CT26 and HCT116 cells through AMPK activation and MAPKs such as ERK, JNK, and p38 inactivation. Moreover, oral administration of SEC decreased pulmonary metastasis of CT26 cells. Our research demonstrates the inhibitory effect of SEC on CRC cell proliferation and metastasis. Thus, SEC might have therapeutic potential for CRC treatment.

Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis

“…The anti-inflammatory potential of CBD has already been confirmed in several models of colitis [17]. However, a study carried out by Nallathambi et al [59] revealed that treatment with purified CBD, at different concentrations (16-252 µg/mL), resulted in a significant decrease in IL-8 levels at lower concentrations of CBD, while no anti-G0/G1 phase arrest, apoptosis (4 µg/mL), cleaved caspase-3 and PARP [88] EtOH extract totic mechanisms in colorectal cancer. , increase; , decrease; 4; CHOP, C/EBP homologous protein; eIF2α, phosphorylated P, poly (ADP-ribose) polymerase; PI3K/Akt, phosphoinositide tive oxygen species; TRPV1, transient receptor potential cation he figure was partly generated using Servier Medical Art, a Creative Commons A ribution 3.0 unported license.…”