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Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies.

Mileo AM, Miccadei S - Oxid Med Cell Longev (2015)

Bottom Line: Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients.Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways.Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.

View Article: PubMed Central - PubMed

Affiliation: Regina Elena National Cancer Institute, 00144 Rome, Italy.

ABSTRACT
Cancer onset and progression have been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation and therefore antioxidant agents could interfere with carcinogenesis. It is well known that conventional radio-/chemotherapies influence tumour outcome through ROS modulation. Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients. To this purpose, many natural polyphenols have emerged as very promising anticancer bioactive compounds. Beside their well-known antioxidant activities, several polyphenols target epigenetic processes involved in cancer development through the modulation of oxidative stress. An alternative strategy to the cytotoxic treatment is an approach leading to cytostasis through the induction of therapy-induced senescence. Many anticancer polyphenols cause cellular growth arrest through the induction of a ROS-dependent premature senescence and are considered promising antitumour therapeutic tools. Furthermore, one of the most innovative and interesting topics is the evaluation of efficacy of prooxidant therapies on cancer stem cells (CSCs). Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways. Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.

No MeSH data available.


Related in: MedlinePlus

Targets of polyphenol anticancer therapies. Epigenetic pathways, cellular redox status, and cancer stem cells as therapeutic targets of polyphenol anticancer therapies as extensively discussed in the text. Depending on acute or chronic treatment a prooxidant activity may induce, respectively, high ROS-mediated cytotoxicity or low ROS-mediated cytostasis. According to the figure, several natural compounds as resveratrol, artichoke polyphenols, ginsenoside Rg-3, and quercetin induce a prooxidant apoptotic mechanism at high concentrations whereas low doses and chronic exposure trigger a ROS-epigenetic mediated cellular senescence.
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Related In: Results  -  Collection


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fig2: Targets of polyphenol anticancer therapies. Epigenetic pathways, cellular redox status, and cancer stem cells as therapeutic targets of polyphenol anticancer therapies as extensively discussed in the text. Depending on acute or chronic treatment a prooxidant activity may induce, respectively, high ROS-mediated cytotoxicity or low ROS-mediated cytostasis. According to the figure, several natural compounds as resveratrol, artichoke polyphenols, ginsenoside Rg-3, and quercetin induce a prooxidant apoptotic mechanism at high concentrations whereas low doses and chronic exposure trigger a ROS-epigenetic mediated cellular senescence.

Mentions: Compared to normal cells, cancer cells have an increased rate of ROS production and have aberrant regulation mechanisms to deal with their particular redox status. ROS have a well-defined role in promoting and maintaining tumorigenicity indicating that dietary antioxidants have an active role in preventing or reducing tumorigenesis. On the other hand, high levels of ROS can also be toxic to neoplastic cells and can potentially induce cell death. Accumulating evidence shows that ROS levels in tumour cells are crucial for designing advanced therapies and future challenge in anticancer treatments. To this purpose, increasing knowledge from epidemiological and experimental data supports the bright future of natural polyphenols as anticancer tools [191–194] (Figure 2). The complex balance among cell proliferation, apoptosis, and senescence induced by polyphenols could be exploited therapeutically to improve the efficacy of conventional cancer treatment and to develop new antitumour strategies (Table 1).


Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies.

Mileo AM, Miccadei S - Oxid Med Cell Longev (2015)

Targets of polyphenol anticancer therapies. Epigenetic pathways, cellular redox status, and cancer stem cells as therapeutic targets of polyphenol anticancer therapies as extensively discussed in the text. Depending on acute or chronic treatment a prooxidant activity may induce, respectively, high ROS-mediated cytotoxicity or low ROS-mediated cytostasis. According to the figure, several natural compounds as resveratrol, artichoke polyphenols, ginsenoside Rg-3, and quercetin induce a prooxidant apoptotic mechanism at high concentrations whereas low doses and chronic exposure trigger a ROS-epigenetic mediated cellular senescence.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663347&req=5

fig2: Targets of polyphenol anticancer therapies. Epigenetic pathways, cellular redox status, and cancer stem cells as therapeutic targets of polyphenol anticancer therapies as extensively discussed in the text. Depending on acute or chronic treatment a prooxidant activity may induce, respectively, high ROS-mediated cytotoxicity or low ROS-mediated cytostasis. According to the figure, several natural compounds as resveratrol, artichoke polyphenols, ginsenoside Rg-3, and quercetin induce a prooxidant apoptotic mechanism at high concentrations whereas low doses and chronic exposure trigger a ROS-epigenetic mediated cellular senescence.
Mentions: Compared to normal cells, cancer cells have an increased rate of ROS production and have aberrant regulation mechanisms to deal with their particular redox status. ROS have a well-defined role in promoting and maintaining tumorigenicity indicating that dietary antioxidants have an active role in preventing or reducing tumorigenesis. On the other hand, high levels of ROS can also be toxic to neoplastic cells and can potentially induce cell death. Accumulating evidence shows that ROS levels in tumour cells are crucial for designing advanced therapies and future challenge in anticancer treatments. To this purpose, increasing knowledge from epidemiological and experimental data supports the bright future of natural polyphenols as anticancer tools [191–194] (Figure 2). The complex balance among cell proliferation, apoptosis, and senescence induced by polyphenols could be exploited therapeutically to improve the efficacy of conventional cancer treatment and to develop new antitumour strategies (Table 1).

Bottom Line: Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients.Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways.Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.

View Article: PubMed Central - PubMed

Affiliation: Regina Elena National Cancer Institute, 00144 Rome, Italy.

ABSTRACT
Cancer onset and progression have been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation and therefore antioxidant agents could interfere with carcinogenesis. It is well known that conventional radio-/chemotherapies influence tumour outcome through ROS modulation. Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients. To this purpose, many natural polyphenols have emerged as very promising anticancer bioactive compounds. Beside their well-known antioxidant activities, several polyphenols target epigenetic processes involved in cancer development through the modulation of oxidative stress. An alternative strategy to the cytotoxic treatment is an approach leading to cytostasis through the induction of therapy-induced senescence. Many anticancer polyphenols cause cellular growth arrest through the induction of a ROS-dependent premature senescence and are considered promising antitumour therapeutic tools. Furthermore, one of the most innovative and interesting topics is the evaluation of efficacy of prooxidant therapies on cancer stem cells (CSCs). Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways. Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.

No MeSH data available.


Related in: MedlinePlus