ABSTRACT
Title
Sulforaphane: a promising example of multi-target therapeutic
Authors
P. Hrelia
Department of Pharmacology, Alma Mater Studiorum-University of Bologna, Bologna , Italy
Abstract
Cancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. To grow, invade and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis.
A great variety of phytochemicals has been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage.
Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents.
Sulforaphane(SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer.
We extensively studied SFN on different in vitro models. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. We also observed that SFN selectively induced cell-cycle arrest and apoptosis in T lymphoblastoid cells but not in non-transformed T cells. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its therapeutic benefit in clinical settings.
These data provide further support for the relevance of SFN as a dietary antitumor agent by showing that SFN can selectively target cancer cells while leaving normal cells virtually unaffected. This selectivity opens the door to a wide range of new scientific questions that will help in understanding the many mechanisms of action for SFN. The data presented here, taken with the previous reports of SFN action, show that SFN can target multiple steps in the carcinogenesis pathway and make it a promising anticancer agent.
A great variety of phytochemicals has been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage.
Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents.
Sulforaphane(SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer.
We extensively studied SFN on different in vitro models. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. We also observed that SFN selectively induced cell-cycle arrest and apoptosis in T lymphoblastoid cells but not in non-transformed T cells. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its therapeutic benefit in clinical settings.
These data provide further support for the relevance of SFN as a dietary antitumor agent by showing that SFN can selectively target cancer cells while leaving normal cells virtually unaffected. This selectivity opens the door to a wide range of new scientific questions that will help in understanding the many mechanisms of action for SFN. The data presented here, taken with the previous reports of SFN action, show that SFN can target multiple steps in the carcinogenesis pathway and make it a promising anticancer agent.
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