In Vitro Studies

Inhibition of cell growth and modulation of the cell cycle have been reported for allyl ITC (AITC) (10 |M), benzyl ITC (BITC) (5 |M), and PEITC (2.5 |M) in HeLa cells,20 and similar effects have been reported for SF (15 |M) in HT-29 cells. Similar results have been reported in other cell lines including human leukemia HL60 and prostate cancer cell lines LNCaP and DU-145 (reviewed by Reference 21). A comprehensive study of the effect of ITCs on the growth of different cancer cells reported that AITC, BITC, and PEITC were able to inhibit cell growth.22 The results of some recent studies are summarized in Table 21.2.

The cytotoxicity of PEITC, BITC, NITC, and SF, as well as the cytotoxicity of the chemotherapeutic agents daunomycin (DNM) and vinblastine (VBL), have been evaluated in human breast cancer MCF-7 and human mammary epithelial

FIGURE 21.4 Cytotoxicity in human breast cancer MCF-7 cells. The effect of varying concentrations of (A) BITC, (B) PEITC, and (C) SF on cell growth of MCF-7/Adr cells following exposure times of (▼) 1 h, (■) 2 h, (A) 3 h, (♦) 6 h, and (•) 48 h. Each data point represents mean ± SE from four wells in one representative study. The study was repeated two to four times. (From Tseng E, Scott-Ramsay EA, Morris ME. Biol Med (Maywood) 2004; 229(8):835-842. Reproduced with permission of the Society for Experimental Biology and Medicine.)

FIGURE 21.4 Cytotoxicity in human breast cancer MCF-7 cells. The effect of varying concentrations of (A) BITC, (B) PEITC, and (C) SF on cell growth of MCF-7/Adr cells following exposure times of (▼) 1 h, (■) 2 h, (A) 3 h, (♦) 6 h, and (•) 48 h. Each data point represents mean ± SE from four wells in one representative study. The study was repeated two to four times. (From Tseng E, Scott-Ramsay EA, Morris ME. Biol Med (Maywood) 2004; 229(8):835-842. Reproduced with permission of the Society for Experimental Biology and Medicine.)

MCF-12A cells23 (Figure 21.4). IC50values for BITC, PEITC, NITC, and SF were 5.95 ± 0.10, 7.32 ± 0.25, 77.9 ± 8.03, and 13.71 ± 0.82 \xM in MCF-7 cells. The corresponding IC50 values for DNM and VBL in MCF-7 cells were 7.12 ± 0.42 \xM and 0.106 ± 0.004 \xM (mean ± SE). Values for BITC, PEITC, NITC, and SF in MCF-12A cells were 8.07 ± 0.29, 7.71 ± 0.07, 33.63 ± 1.69, and 40.45 ± 1.25 |M, respectively. BITC and PEITC can inhibit the growth of human breast cancer cells as well as human mammary epithelium cells, at concentrations similar to the chemotherapeutic drug DNM. SF and NITC exhibited higher IC50 values. These concentrations are four- to sixfold lower than the IC50 for the isoflavonoid,

FIGURE 21.4 (CONTINUED)

genistein, a compound that has also been studied in MCF-7 cells. Genistein has been reported to have the lowest IC50 among the dietary flavonoids tested in MCF-7 cells.24

While some studies have demonstrated similar cytotoxicity in cancer and normal cells,23,25 others have reported differences. A synthetic ITC 4-(methylthio) butyl ITC has shown selective action against human leukemia cells, and almost no effect on lymphocytes.26 AITC also has an inhibitory effect in the human prostate cancer cell lines, while normal cell line PrEC remained unaffected by the same exposure.27

The cytotoxic effects of ITCs are apparent even after shorter exposures. Comprehensive time-dependent studies of the effect of ITCs on the growth of different cell lines reported that a number of ITCs, including AITC, BITC, PEITC, and NITC, were able to inhibit cell growth after 2- or 3-h exposures, producing IC50 values similar to those for exposure for 48 to 72 h, indicating that short-term exposure is sufficient to produce an observable effect in vitro.22,23

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