Alhosin et al. Journal of Experimental & Clinical Cancer Research 2011, 30:41 http://www.jeccr.com/content/30/1/41 Page 7 of 10 Figure 4 Summary of the effects of natural products such as TQ and RWPs. These compounds are putative “regulators” of the epigenetic code inheritance, since they are able to target UHRF1 with a subsequent cell cycle arrest, apoptosis and tumor vascularization reduction. An open square containing a question mark, emphases the possibility that numerous other natural compounds can take the same pathways leading to apoptosis. apoptosis in colorectal cancer by activation of p53 and p73 which are negative upstream regulators of UHRF1 [46,67]. These findings suggest that RWPs exert their antitumoral activities in colorectal cancer through a mechanism of feedback control involving TSGs and UHRF1 (Figure 3B). Thus, targeting UHRF1 by natural compounds could be an interesting way to prevent and/ or to treat colorectal cancers. Combination of HDACs and DNMT1 inhibitors exhi- bits synergic anti-neoplasic effect for different types of cancer [100-103]. A phase I pilot study showed that chronic intake of black raspberries by patients suffering from colorectal cancers leads to down-regulation of DNMT1 and re-expression of TSGs through a DNA demethylating process [104]. This suggests that a thera- peutically-induced inhibition of UHRF1 activity or expression could prevent the action of its preferred part- ners, HDAC1 and DNMT1, leading to a re-expression of the tumour suppressor genes p16INK4A and thus allow- ing the cancer cells to undergo apoptosis. Conclusion Natural compounds such as TQ, RWPs and potentially others (Figure 4) are triggering a series of events that involve cell cycle arrest, apoptosis and inhibition of angiogenesis, all under the control of UHRF1. UHRF1 is a key component of a macro-molecular complex includ- ing among others HDAC1, DNMT1, Tip60 and HAUSP, responsible for the epigenetic code duplication after DNA replication. UHRF1 behaves as a conductor in this replication by performing a crosstalk between DNA methylation and histone modifications. This allows cancer cells to maintain their pathologic repression of TSGs during cell proliferation. This review supports the paradigm that UHRF1 is a potential target for cancer prevention and therapy, since its repression may lead to the re-expression of TSGs, allowing cancer cells to undergo apoptosis. Natural anticancer products have been shown to suppress the expression of UHRF1. This suggests that these chemo-preventive and chemothera- peutic compounds potentially have the virtues to repair the “wrong” epigenetic code in cancer cells by targeting the epigenetic integrator UHRF1. It is very legitimate to propose that down-regulation of UHRF1 by natural compounds is a key event in their mechanism of action, considering that re-expression of tumor suppressor genes in cancer cells is dependent upon demethylation of their promoters and that UHRF1 is involved in the maintenance of DNA methylation patterns. These stu- dies also highlight that UHRF1 and its partners are putative targets for the adaptation to environmental fac- tors, such as diet. We also do not exclude that the beha- vior of the epigenetic code replication machinery, ECREM, might influence transgenerational message of environmental factors. Authors’ contributions MA and CB designed the review and drafted part of it. TS, MM, NES, GF and VBSK equally contributed to the writing the other part of the review. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. 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