Effects of β-caryophyllene on arginine ADP-ribosyltransferase 1-mediated regulation of glycolysis in colorectal cancer under high-glucose conditions

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of the development of colorectal cancer (CRC). A previous study revealed that the levels of arginine-specific mono-ADP-ribosyltransferase 1 (ART1) in CRC tissues from patients with T2DM were higher than in non-diabetic patients. Hyperglycemia, which is a risk factor of cancer, is a common feature of T2DM; however, the effects of ART1 on glycolysis and energy metabolism in CRC cells under high-glucose conditions remains to be elucidated. β-caryophyllene (BCP) has been reported to exert anticancer and hypoglycemic effects. In the present study, CT26 cells were cultured under a high-glucose conditions and the expression levels of relevant factors were detected by western blotting. Cell Counting Kit-8 assay, flow cytometry, Hoechst 33258 staining, ATP assay and lactic acid assay were used to detect the proliferation, apoptosis and energy metabolism of CT26 cells. To observe the effects of ART1 and BCP on tumor growth in vivo, CT26 cell tumors were successfully transplanted into BALB/c mice with T2DM. The results demonstrated that overexpression of ART1 may increase glycolysis and energy metabolism in CT26 CRC cells under high glucose conditions by regulating the protein kinase B/mammalian target of rapamycin/c‑Myc signaling pathway and the expression of glycolytic enzymes. BCP inhibited the effects induced by ART1, which may be due to a BCP-induced reduction in the expression levels of ART1 via nuclear factor-κB. Therefore, ART1 may be considered a therapeutic target for the treatment of diabetic patients with CRC.

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

“…The overexpression of ART1 probably increases glycolysis and energy metabolism, thus regulating the protein kinase B/mammalian target of rapamycin/c-Myc signaling pathway and the expression of glycolytic enzymes. This suggests that BCPO may be a potential treatment for this kind of carcinoma [51].…”

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

“…Furthermore, it produces cytoprotective effects by modulating oxidative stress, apoptosis and inflammation [38][39][40][41], through the interference with different inflammatory pathways, such as the inducible nitric oxide synthase (iNOS), tumor necrosis factor-alfa (TNF-α) and nuclear factor-κB (NF-κB) [37]. Also, it exhibited chemopreventive properties, such as genoprotective and antiproliferative ones, by inhibiting DNA damage and STAT3 (signal transducer and activator of transcription 3) activation induced by environmental pollutants [31,32,42,43] and through affecting multiple cascades involved in cancer growth [37,[44][45][46][47]. Similar properties have been also reported for the metabolite β-caryophyllene oxide [48,49].…”

Ferulago nodosa Subsp. geniculata (Guss.) Troia & Raimondo from Sicily (Italy): Isolation of Essential Oil and Evaluation of Its Bioactivity

“…Zhou et al [ 45 ] suggested, also, that β-caryophyllene could be used as a therapeutic target for the treatment of diabetic patients, since this terpene acts at the level of arginine-specific mono-ADP-ribosyltransferase 1. Moreover, β-caryophyllene oral administration at a dose of 200 mg/kg induced a reduction of glucose, increase of plasma insulin levels, and improvement of altered activities of carbohydrate metabolic enzymes [ 46 ].…”