GA 2017

Normal cells rapidly undergo apoptosis when lose adhesion or relocate to an inadequate environment, in a process termed anoikis. In cancer, anoikis-resistant ability is a key feature that promotes survival of metastatic cancer cells. Isothiocyanates (ITCs) are natural compounds present in cruciferous vegetables like broccoli, cabbage, and cauliflower. Previous studies showed that ITCs exhibit a protective effect against various types of cancer such as lung cancer, esophagitis, breast cancer, hepatocellular carcinoma, and colon cancer. In the present study, three common ITCs, sulforaphane (1), benzyl isothiocyanate (2), and phenethyl isothiocyanate (3) were investigated for the their ability to reduce anoikis resistance in non-small cell lung cancer (NSCLC) A549 and CL1-5 cells. A549 and CL1-5 cells were cultured in ultra-low attachment dishes to prevent cell attachment and treated with ITCs for 72 hours. Among them, 1 was the most potent in inhibiting cell viability in suspending A549 and CL1-5 cells. Of note, 1 had a less effect on the monolayer growth of adherent cells, indicating a selective inhibition of anchorage-independent cell growth. In addition, SFN induced anoikis of suspending A549 and CL1-5 cells, which was identified by nuclear condensation, annexin V binding, activation of caspases, and cleavage of PARP. Investigating the action of mechanism of SFN revealed that SFN inhibited focal adhesion kinase (FAK) and Akt activation, upregulated the cyclin-dependent kinase inhibitor p21 as well as the pro-apoptotic proteins Bax and Bad. Taken together, our results indicate that dietary ITCs, especially 1, are able to restore the sensitivity of NSCLC to anoikis, and suggest a potential benefit of ITCs for prevention or treatment of metastatic lung cancer.