EZH2 (associated with metastasis and poor prognosis in cancer patients) in breast
cancer cells (Dimri et al. 2010).
The cross-resistance profile of 60 tumor cell lines was analyzed using inhibitori
50 % concentration (IC 50 ) of eight different withanolides (the major secondary
metabolites of Withania somnifera) and 19 established anticancer drugs (Efferth
and Greten 2012). The cell lines revealed cross-resistance between the eight
withanolides. Consistent cross-resistance between withanolides and nitrosoureas
was also observed. Then the authors performed transcriptomic microarray-based
COMPARE and hierarchical cluster analyses of mRNA expression to identify
mRNA expression profiles predicting sensitivity or resistance toward withanolides.
Genes from diverse functional groups were significantly associated with response
of tumor cells to withaferin A diacetate, e.g., genes functioning in DNA damage
and repair, stress response, cell growth regulation, extracellular matrix.
Another compound related with beneficial health in cancer is iodine, since it
induces apoptosis by regulating MAPKs (Mitogen-Activated Protein Kinase)related p53, p21, and Bcl-xL in thyroid cancer cells (Liu et al. 2010). One study
comparing the proliferative properties of genistein and daidzein, demonstrated
modulations of cyclin-dependent kinase-related pathway genes, DNA damage
signaling pathway and a downregulation of EGF and IGF on human prostate
cancer cell leading to cell cycle arrest (Rabiau et al. 2010).
Only few dietary components among hundreds that have been proposed as
potential cancer preventive agents have been used in clinical trials. The impact of
lycopene supplementation has been studied in a crossover design with 30 healthy
men. Talvas et al. (2010) showed that cancer prostatic cell incubation with sera
from men who consumed purified lycopene (from tomato), led to significant
upregulation of IGFBP-3, c-fos, uPAR, and Bax:Bcl-2 ratio, and downregulation of
cyclin-D1, p53, and Nrf-2 compared with sera collected after placebo consumption, inducing apoptosis and cell cycle arrest. Multivitamins, folate, and green
vegetables have been suggested to protect against gene promoter methylation in
the aerodigestive tract of smokers (Stidley et al. 2010). Published population-based
cases of rectal cancer (Slattery et al. 2010) concluded that fat-rich dairy products
might be associated with an increased risk of CIMP+ (CpG Island Methylator
Phenotype) tumors, while low-fat dairy products reduced risk of CIMP+ . Omega3 fatty acids were associated with an increased risk of a CIMP+ tumor. High levels
of vegetable intake reduced risk of both TP53 and KRAS2 mutations. High intake
of whole grains reduced the likelihood of a TP53 mutation, whereas high intake of
refined grains increased the likelihood of a TP53 mutation. Dietary fiber was also
associated with reduced risk of TP53 and KRAS2 rectal tumor mutations. These
data suggest that diet is associated with specific types of rectal tumor mutations
and epigenetic changes.
Epidemiological and preclinical evidence continues to highlight dietary components ranging from macro- to micro-constituents as likely modifiers of cancer
processes.
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