NOS2 and digestive system neoplasm: In another study, Vanamala and coworkers [139] showed that grapefruit juice and limonin produce suppressive effects on AOM-induced colon carcinogenesis by lowering inducible nitric oxide synthases iNOS and cyclooxygenase-2 COX-2 levels and upregulating apoptosis, thereby reducing the formation of aberrant crypt foci.