Cell cycle arrest and apoptosis induction by Juniperus communis extract in esophageal squamous cell carcinoma through activation of p53‐induced apoptosis pathway

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. It has a high mortality rate and requires novel effective drugs and therapeutic approaches. Juniperus communis (JCo), used to flavor gin and food, has been documented to have anti‐tumor activity. The aim of this study was to investigate the antitumor activity of JCo extract against ESCC and its possible mechanisms. JCo extract suppressed cell growth in ESCC and showed higher selection for ESCC cells than normal cells compared to the clinical drug 5‐fluorouracil (5‐FU). JCo extract induced cell cycle arrest at the G(0)/G(1) phase by regulating the expression of p53/p21 and CDKs/cyclins, triggering cell apoptosis by activating both the extrinsic (Fas/FasL/Caspase 8) and intrinsic (Bcl‐2/Bax/Caspase 9) apoptosis pathways. Moreover, a combination treatment of JCo and 5‐FU synergistically inhibited proliferation of ESCC cells. These results suggest that JCo extract is a potential natural therapeutic agent for esophageal cancer, as it could induce cell cycle arrest and apoptosis in ESCC cells.