Echinatin induces reactive oxygen species‐mediated apoptosis via JNK/p38 MAPK signaling pathway in colorectal cancer cells

Abstract

Colorectal cancer (CRC) is a very common and deadly cancer worldwide, and oxaliplatin is used as first‐line chemotherapy. However, resistance usually develops, limiting treatment. Echinatin (Ech) is the main component of licorice and exhibits various therapeutic effects on inflammation‐mediated diseases and cancer, ischemia/reperfusion, and liver injuries. The present study elucidated the underlying molecular mechanism of Ech‐induced apoptosis in both oxaliplatin‐sensitive (HT116 and HT29) and ‐resistant (HCT116‐OxR and HT29‐OxR) CRC cells. To evaluate the antiproliferative activities of Ech, we performed MTT and soft agar assays. Ech reduced viability, colony size, and numbers of CRC cells. The underlying molecular mechanisms were explored by various flow cytometry analyses. Ech‐induced annexin‐V stained cells, reactive oxygen species (ROS) generation, cell cycle arrest, JNK/p38 MAPK activation, endoplasmic reticulum (ER) stress, mitochondrial membrane potential depolarization, and multi‐caspase activity. In addition apoptosis‐, cell cycle‐, and ER stress‐related protein levels were confirmed by western blotting. Moreover, we verified ROS‐mediated cell death by treatment with inhibitors such as N‐acetyl‐L‐cysteine, SP600125, and SB203580. Taken together, Ech exhibits anticancer activity in oxaliplatin‐sensitive and ‐resistant CRCs by inducing ROS‐mediated apoptosis through the JNK/p38 MAPK signaling pathway. This is the first study to show that Ech has the potential to treat drug‐resistant CRC, providing new directions for therapeutic strategies targeting drug‐resistant CRC.

Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis

“…To further explore the mechanism by which TS-inhibited UC, we examined the expression of NF-κB and MAPK signaling access associated proteins, which play an important role in promoting inflammation cytokines production [ 47 , 48 ]. NF-κB and MAPK are cellular access that mainly promote the production of inflammation and have a tremendous impact on the production of cytokines.…”

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

“… 73 Echinatin can protect against arterial stiffening 74 and induce apoptosis in colorectal cancer cells lines HT116 and HT29. 75 Loureirin A, found in dragon’s blood 76 was used to promote blood circulation and can relieve arthritis pain in mice. 77 The potency of these compounds in our model makes them potentially interesting candidates for estrogen replacement therapies/supplements.…”

Licochalcone B Induces ROS-Dependent Apoptosis in Oxaliplatin-Resistant Colorectal Cancer Cells via p38/JNK MAPK Signaling

“…LCA, a licorice extract from a similar family, induced ROS-dependent apoptosis in CRC [ 29 ]. Another previously reported licorice extract, echinatin, also induced apoptosis via the ROS-mediated JNK/p38 MAPK signaling pathway in CRC [ 30 ]. ROS and free radicals have been reported to directly induce DNA damage via oxidized nucleoside bases, such as 8-oxoguanine formation [ 31 ].…”