Identification of novel compounds in Undaria pinnatifida with anti-cancer potential

In New Zealand, the rate of registered cancer cases increased significantly in recent years especially for breast, melanoma, colorectal cancer and lung cancer (Ministry of Health, 2008b). The success rate of cancer chemotherapy is generally low mainly due to cytotoxic side effects and multi-drug resistance of current anti-cancer drugs (Szakács, Paterson, Ludwig, Booth-Genthe, & Gottesman, 2006). Two major components of U. pinnatifida, fucoxanthin and fucoidan, have recently been found to induce apoptosis in various cancer cell lines (Nishibori, Itoh, Kashiwagi, Arimochi, & Morita, 2012). The primary objective of this study was to investigate whether fucoxanthin could inhibit proliferation of different types of cancer cells in a time- and concentration-dependant pattern. The secondary objective of this study was to determine other potential anti-cancer compounds from both New Zealand and Japanese U. pinnatifida. In addition, a novel extraction method has been developed by Japanese scientists to isolate fucoxanthin and fucoidan by supercritical carbon dioxide and subcritical water in a single process. The third purpose was to evaluate biological activities of these two major components isolated by using the novel extraction method. Based on the particular statistical reported several types of human cancer cell lines were used in this study including lung carcinoma A549, NCI-H522, colon adenocarcinoma WiDr, Lovo, hepatocellular carcinoma Hep G2, breast adenocarcinoma MCF-7, malignant melanoma Malme-3M, cervix squamous carcinoma SiHa, and neuroblastoma SK-N-SH. Anti-proliferative effects were determined by 24 hr-72 hr MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. Pure fucoxanthin showed anti-proliferative effects in all types of cancer cell lines in dose- and time- dependent manners. The ranking of anti-proliferative sensitivity to fucoxanthin is in the order of SiHa > MCF-7, Lovo, NCI-H522 > Hep G2, A549, WiDr, SK-N-SH, and Malme-3M. Similarly, anti-proliferative effects of fucoxanthin extracted from New Zealand seeweeds were found in all types of cancer cell lines in dose- and time- dependent manners. These three fucoxanthin extracts (purity of fucoxanthin: 0.2%, 43.5% and 60.77%) were achieved through a series of fucoxanthin isolation and purification procedures. Compared with anti-proliferative IC50 of pure fucoxanthin standards, the significant anti-proliferative effects of fucoxanthin extracts were found in some cancer cell lines including WiDr, Lovo, and NCI-H522. Similar results were also found from the determination of anti-proliferative effects fucoxanthin extracts by the novel extraction method. However, SiHa and Malme-3M were special cases, suggesting some of compounds might effectively inhibit growth of those cancer cells. In comparison to other published studies, similar anti-proliferative effects from Japanese fucoidan fraction were found in dose- and time dependence, but its anti-proliferative effects were much lower. In conclusion, fucoxanthin as a type of marine carotenoid possessed effectively anti-proliferative effects to multiple types of cancer cell lines. Thus, fucoxanthin can be the important phytochemical with chemopreventive effects. Furthermore, some of novel compounds with potential anti-cancer effects might be contained in New Zealand and Japanese U. pinnatifida. This suggested U. pinnatifida as part of a human diet could possibly decrease the risk of cancer especially for human cervix, colon and lung cancer. Finally, crude fucoxanthin was successfully isolated by supercritical carbon dioxide from novel extraction method. However, fucoidan fraction which possessed biological anti-cancer activity might not be obtained from extract using subcritical water