Progress 10/01/00 to 09/30/06
Outputs
This research project focused on evaluating the effect of plant constituents as cancer preventive agents. Specifically, two phytochemicals, one in cruciferous vegetables (the isothiocyanate sulforaphane) and one in soybeans (soyasaponin), were examined for their capacity to act as inhibitors of breast and colon cancer, respectively. The cruciferous phytochemical sulforaphane was found to act on human breast cancer cells in a novel manner by disrupting cellular structures (called the mitotic spindles) that are crucial to the division or multiplication of these cells. Sulforaphane blocked the orderly multiplication of these cells in a way that lead to cell death. Soyasaponins on the other hand were found to stimulate in human colon cancer cells a novel form of programmed cell death called autophagy. This action of soyasaponins in stimulating autophagy is a newly identified effect of soyasaponins on colon cancer cells, and was effective at levels of soyasaponins that
could be attainable from dietary consumption of soy products.
Impacts
This research provides new leads in characterizing the anticancer actions of these two commonly consumed foods. The information from this research project should contribute to efforts to use these phytochemicals in breast and colon cancer prevention strategies.
Publications
- Ellington, A., Berhow, M. and Singletary, K. 2006. Inhibition of Akt signaling and enhanced ERK1/2 activity are involved in induction of macroautophagy by triterpenoid B-group soyasaponins in colon cancer cells. Carcinogenesis 27: 298-306.
- Ellington, A., Singletary, K. and Berhow, M. 2005. Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins. Carcinogenesis 26: 159-167.
- Jackson, S. and Singletary, K. 2004. Sulforaphane inhibits human MCF-7 mammary cancer cell proliferation and tubulin polymerization. Journal Nutrition 134: 2229-2236.
- Jackson, S. and Singletary, K. 2004. Sulforaphane: A naturally-occurring mammary carcinoma mitotic inhibitor which disrupts tubulin polymerization. Carcinogenesis 25: 219-227.
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Progress 01/01/05 to 12/31/05
Outputs
The crudiferous vegetables, which include broccoli and similar plants, have deen identified as possessing phytochemicals called isothiocyanates that have cancer protective properites. We have evaluated the effectiveness of these isothiocyanates as inhibitors of breast cancer. When both animal and human breast cancer cells were treated with the isothiocyanate sulforaphane, there was a marked blockage of cell multiplication. This effect of sulforaphane was noted not only in cell culture studies, but also in an animal model for breast cancer. Furthermore, a new mechanism of action of sulforaphane was discovered, as a disruptor of the function of cell structural proteins called microtubules. This action of sulforaphane is similar to that of a class of cancer drugs currently used in therapy, called mitotic inhibitors. Currently, additional studies are being conducted to better characterize the inhibitory effect of sulforaphane on human breast cancer cells.
Impacts
Americans are being encouraged to increase consumption of plant foods so as to decrease their risk for various chronic diseases including cancer. Our findings with sulforaphane support this recommendation and highlight another benefit that cruciferous vegetable intake may have in opposing cancer development. Information from these studies also may contribute to the development of cancer prevention strategies in which natural products alone and in combination with drugs may be used to increase cancer inhibitory effectiveness with fewer unwanted side effects.
Publications
- Jackson, J. and Singletary, K. 2004. Sulforaphane: A naturally occurring mammary carcinoma mitotic inhibitor which disrupts tubulin polymerization. Carcinogenesis 25: 219-227.
- Jackson, J. and Singletary, K. 2004. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J. Nutr. 134: 2229-2236.
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Progress 01/01/04 to 12/31/04
Outputs
Sulforphane is a phytochemical released into the body when cruciferous vegetables, such as broccoli, are consumed. We studied the impact of sulforaphane treatment on the multiplication of human and mouse breast cancer cells. For both, sulforaphane treatment of cell cultures led to a suppression of cancer cell division. Sulforaphane, when administered to mice, also retarded the growth of their breast tumors. A novel aspect of these findings is that sulforaphane blocked cell multiplication by disrupting the formation of cell structures, called microtubules, that are important for the orderly process of cell division. This disruption of tubulin polymerization is a mechanism similar to a class of cancer chemotherapy drugs, such as vinblastine or taxol. These findings indicate that sulforaphane has antiproliferative effects on breast cancer cells that may be useful in cancer chemoprevention strategies.
Impacts
These findings highlight new processes by which this specific vegetable component can have benefit in retarding breast cancer cell growth, and opens up new avenues of investigation for using this phytochemical in breast cancer chemoprevention strategies.
Publications
- Jackson, S. and Singletary, K. 2004. Sulforaphane inhibits human MCF-7 mammary cancer cell proliferation and tubulin polymerization. Journal of Nutrition 134: 2229-2236.
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Progress 01/01/03 to 12/31/03
Outputs
This research has focused on characterizing a potentially new mechanism whereby sulforaphane, an isothiocyante compound from cruciferous vegetables, could retard the proliferation of human breast cancer cells. In cell culture studies we determined that sulforaphane blocked cell multiplication at a specific stage of cell division (prometaphase)and appeared to do so by disrupting the process of chromosome rearrangement (tubulin polymerization). This blockage was associated with alterations in cell cycle regulatory proteins and enhancement of programmed cell death. Subsequently, the breast cancer cell inhibitory action of sulforaphane was confirmed in an animal model.
Impacts
These findings highlight new processes by which this specific vegetable component can have benefit in retarding breast cancer cell growth, and opens up new avenues of investigation for using this phytochemical in breast cancer chemoprevention strategies.
Publications
- Jackson, S.J.T. and Singletary, K.W. 2003. Sulforaphane: A naturally-occurring mammary carcinoma mitotic inhibitor which disrupts tubulin polymerization. Carcinogenesis 24: 1-9.
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Progress 01/01/02 to 12/31/02
Outputs
The cancer suppressive action of two plant phytochemicals were evaluated, sulforaphane (a constituent of cruciferous vegetables)and a soy saponin extract. Sulforaphane, at concentrations less than 15 micromolar, was found to be an effective inhibitor of cell cycle progression when tested with mouse and human breast cancer cell lines. Also, when sulforaphane (in nanomole quantities) was administered to mice implanted with syngeneic breast carcinoma cells, there was a significant decrease in the in vivo growth of the tumors. Sulforaphane blocked cell division within the M stage, and concurrently induced apoptosis. A soy saponin fraction was tested in separate experiments for its inhibitory action toward the multiplication of human colon cancer cellsn vitro. The soy saponin extract blocked cell proliferation at low microgram concentrations when added to cultures of colon cancer cells. Of particular interest is that this extract stimulated a novel, nonapoptotic cell death
pathway in these colon cancer cells leading to their disintegration.
Impacts
Results from these experiments indicate that these two phytochemicals have considerable promise for use in cancer chemoprevention strategies. Both phytochemicals demonstrated significant effects at physiologicallly relevant concentrations. Clarification of their dose and time-related actions as well as a clearer understanding of their mechanisms of action should lead to inclusion of these natural products in dietary protocols for preventing cancer.
Publications
- No publications reported this period
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Progress 01/01/01 to 12/31/01
Outputs
Studies were conducted to determine the capacity of select phytochemicals to inhibit the growth of a highly cancerous mouse mammary cell line. Based on a screen of a variety of phytochemicals from several plant sources, we identified the cruciferous vegetable constituent sulforaphane to be one of the most potent inhibitors. Subsequent experiments have determined that sulforaphane is an effective inducer of a specific cell cycle block and of programmed cell death (apoptosis). The molecular markers of cancer development that are being modulated by sulforaphane are presently being identified and characterized.
Impacts
These studies provide further clarification of the molecular mechanisms contributing to the cancer-protective actions of vegetable consumption that have been reported in numerous epidemiological reports. In addition, the potential use of sulforaphane and similar phytochemicals in strategies for breast cancer prevention warrants further investigation.
Publications
- No publications reported this period
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Progress 01/01/00 to 12/31/00
Outputs
Select phytochemicals have been screened to determine their antiproliferative effect on metastatic mouse mammary cancer cells. Particularly potent were specific isothiocyanates found in vegetables. This cell growth inhibitory action was associated with alterations in cellular proteins controlling cell cycle progression and programmed cell death (apoptosis). Studies are in progress to characterize these cancer inhibitory effects.
Impacts
Increased fruit and vegetable consumption is associated with reduced risk for numerous cancers. This project will examine the effectiveness of select phytochemicals as suppressors of breast and colon cancer in cell culture and animal models.
Publications
- No publications reported this period
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