Bergamottin (BGM) is a naturally occurring furanocoumarin and is known to inhibit the growth of tumor cells. However, there is no available evidence that BGM has an inhibitory effect on cancer metastasis, specifically on the epithelial-to-mesenchymal transition (EMT) process in the malignant cells. Here we aimed to evaluate the antimetastatic potential of BGM in human lung adenocarcinoma cells. Our results demonstrate that BGM can block EMT, and observed inhibition was accompanied by downregulation of fibronectin, vimentin, N-cadherin, twist and snail expression, and upregulation of occludin and E-cadherin. Interestingly, transforming growth factor-β (TGF-β)-induced upregulation of fibronectin, vimentin, N-cadherin, twist and snail, and downregulation of occludin and E-cadherin, were abrogated by BGM treatment. Moreover, the treatment of BGM repressed TGF-β-induced cell invasive potential. BGM treatment also inhibited multiple oncogenic cascades such as PI3K/Akt/mTOR. Overall, the results demonstrate the potential antimetastatic activity of BGM against lung cancer cells. Full article

Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer. Full article

Despite tremendous progress made during the last few decades in the treatment options for cancer, compounds isolated from Mother Nature remain the mainstay for therapy of various malignancies. Fangchinoline, initially isolated from the dried root of Stephaniae tetrandrine, has been found to exhibit diverse pharmacological effects including significant anticancer activities both in tumor cell lines and selected preclinical models. This alkaloid appears to act by modulating the activation of various important oncogenic molecules involved in tumorigenesis leading to a significant decrease in aberrant proliferation, survival and metastasis of tumor cells. This mini-review briefly describes the potential effects of fangchinoline on important hallmarks of cancer and highlights the molecular targets modulated by this alkaloid in various tumor cell lines and preclinical models. Full article