Dietary isothiocyanates reduce anoikis resistance of non-small cell human lung cancer cells

• Main Authors: Shin-Han Tsai, 蔡昕翰
• Other Authors: Chin-Chung Wu
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/70657732275785618509

碩士 === 高雄醫學大學 === 天然藥物研究所碩士班 === 104 === ells rapidly undergo apoptosis when relocate to an inadequate environment or loss of cell-matrix adhesion, in a process termed anoikis. Anoikis plays a vital role in the regulation of cancer metastasis which can inhibit tumor growth. In non-small cell lung cancers (NSCLCs), anoikis-resistant capability is the key step that enables cancer cells to succeed in their colonization at the secondary site. Isothiocyanates (ITCs) are natural compounds present in cruciferous vegetables (Brassicaceae) 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. Sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC) are the most well-known ITCs in cancers studies. For investigating whether ITCs reduce anoikis resistance in NSCLCs, human lung cancer A549 and CL1-5 cells were cultured in specially treated ultra-low culture dishes and treated with ITCs for 72 hours. ITCs inhibited cell viability in suspending A549 and CL1-5 cells, but had a less effect on the monolayer growth of adherent cells by using MTS assay. In addition, the inhibition of anchorage-independent growth by ITCs was observed by using sphere formation assay. SFN induced apoptosis of suspending A549 and CL1-5 cells which was identified by formation of DNA ladder, activation of casepase-3 and cleavage of PARP. Investigating the action of mechanism of SFN revealed that SFN inhibited FAK phosphorylation, reduced 14-3-3ζ and anti-apoptotic Bcl-2 proteins, as well as increased pro-apoptotic proteins. Taken together, our results indicate that ITCs can restore the sensitivity of NSCLCs to anoikis, and suggest a potential benefit of ITCs for treatment of metastatic lung cancer.