Limits...
Molecular Mechanisms and Therapeutic Effects of (-)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration.

Shay J, Elbaz HA, Lee I, Zielske SP, Malek MH, Hüttemann M - Oxid Med Cell Longev (2015)

Bottom Line: This paper reviews the biological effects of a group of natural compounds called polyphenols, including apigenin, epigallocatechin gallate, genistein, and (-)-epicatechin, with a focus on the latter. (-)-Epicatechin has several unique features responsible for a variety of its effects.One of these is its ability to interact with and neutralize reactive oxygen species (ROS) in the cell. (-)-Epicatechin also modulates cell signaling including the MAP kinase pathway, which is involved in cell proliferation.This paper discusses the potential of some phenolic compounds to maintain, protect, and possibly reinstate health.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA ; Karmanos Cancer Institute, Detroit, MI 48201, USA.

ABSTRACT
With recent insight into the mechanisms involved in diseases, such as cardiovascular disease, cancer, stroke, neurodegenerative diseases, and diabetes, more efficient modes of treatment are now being assessed. Traditional medicine including the use of natural products is widely practiced around the world, assuming that certain natural products contain the healing properties that may in fact have a preventative role in many of the diseases plaguing the human population. This paper reviews the biological effects of a group of natural compounds called polyphenols, including apigenin, epigallocatechin gallate, genistein, and (-)-epicatechin, with a focus on the latter. (-)-Epicatechin has several unique features responsible for a variety of its effects. One of these is its ability to interact with and neutralize reactive oxygen species (ROS) in the cell. (-)-Epicatechin also modulates cell signaling including the MAP kinase pathway, which is involved in cell proliferation. Mutations in this pathway are often associated with malignancies, and the use of (-)-epicatechin holds promise as a preventative agent and as an adjunct for chemotherapy and radiation therapy to improve outcome. This paper discusses the potential of some phenolic compounds to maintain, protect, and possibly reinstate health.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of epigallocatechin gallate, genistein, apigenin, and (−)-epicatechin and its oxidation product (−)-epicatechin-o-quinone.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4477097&req=5

fig1: Chemical structures of epigallocatechin gallate, genistein, apigenin, and (−)-epicatechin and its oxidation product (−)-epicatechin-o-quinone.

Mentions: Epigallocatechin gallate (EGCG) (Figure 1) is the most abundant catechin found in green tea (Camellia sinensis) [6]. EGCG is a potent antioxidant that has various clinical applications. It is a widely studied catechin in cancer research and the potential underlying mechanisms have started to emerge. As an example, Lin et al. [7] demonstrated that treatment with EGCG inactivated the STAT3 pathway, which plays a critical role in promoting tumor formation in tumor initiating cells of nasopharyngeal carcinoma. The study showed a reduction in the stemness of tumor initiating cells by sphere formation, colony formation, cell viability, and an increased sensitivity to cisplatin, indicating that the compound directly affects growth signaling in cancer cells. Mukherjee et al. [8] reported that EGCG is able to sequester the p65 subunit of the transcription factor NF-κB and to inhibit cytokine and chemokine transcription following CpG synthetic oligodeoxynucleotide treatment in DU145, PC3, and LNCaP prostate cancer cell lines. This suggests that EGCG is able to ameliorate chronic inflammation resulting from microbial pathogens that increases the risk for prostate cancer. Poutahidis et al. [9] observed that ApcMin/+ mutant mice, upon gastrointestinal tract infection with Helicobacter hepaticus, were significantly predisposed to prostate cancer, suggesting that infection-mediated inflammation can drive cancer progression. EGCG was further found to decrease protein expression of both HIF-1α and its downstream target vascular endothelial growth factor (VEGF) in MCF-7 cells in a dose-dependent manner [10]. In addition, EGCG was found to protect the cells from ionizing radiation. A recent study showed that, with a simple pretreatment of 50 μM EGCG, human epidermal keratinocytes (HaCaT cell line) were protected from radiation-induced (20 Gy) cytotoxicity [11]. This was demonstrated by a reduction in (1) apoptotic cells as analyzed by flow cytometry of annexin V/propidium iodide double staining, (2) damage to the mitochondria analyzed by MitoTracker Red staining and upregulation of superoxide dismutase 2, (3) total cellular ROS as determined by DCFDA staining, and (4) γH2AX foci, a marker of DNA damage [11]. They also observed an EGCG-dependent transcriptional induction of heme oxygenase-1, which the authors concluded to be the primary source of the protective effect. After treatment with EGCG following either siRNA knockdown or use of a specific inhibitor of heme oxygenase-1, the protective effects diminished [11].


Molecular Mechanisms and Therapeutic Effects of (-)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration.

Shay J, Elbaz HA, Lee I, Zielske SP, Malek MH, Hüttemann M - Oxid Med Cell Longev (2015)

Chemical structures of epigallocatechin gallate, genistein, apigenin, and (−)-epicatechin and its oxidation product (−)-epicatechin-o-quinone.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4477097&req=5

fig1: Chemical structures of epigallocatechin gallate, genistein, apigenin, and (−)-epicatechin and its oxidation product (−)-epicatechin-o-quinone.
Mentions: Epigallocatechin gallate (EGCG) (Figure 1) is the most abundant catechin found in green tea (Camellia sinensis) [6]. EGCG is a potent antioxidant that has various clinical applications. It is a widely studied catechin in cancer research and the potential underlying mechanisms have started to emerge. As an example, Lin et al. [7] demonstrated that treatment with EGCG inactivated the STAT3 pathway, which plays a critical role in promoting tumor formation in tumor initiating cells of nasopharyngeal carcinoma. The study showed a reduction in the stemness of tumor initiating cells by sphere formation, colony formation, cell viability, and an increased sensitivity to cisplatin, indicating that the compound directly affects growth signaling in cancer cells. Mukherjee et al. [8] reported that EGCG is able to sequester the p65 subunit of the transcription factor NF-κB and to inhibit cytokine and chemokine transcription following CpG synthetic oligodeoxynucleotide treatment in DU145, PC3, and LNCaP prostate cancer cell lines. This suggests that EGCG is able to ameliorate chronic inflammation resulting from microbial pathogens that increases the risk for prostate cancer. Poutahidis et al. [9] observed that ApcMin/+ mutant mice, upon gastrointestinal tract infection with Helicobacter hepaticus, were significantly predisposed to prostate cancer, suggesting that infection-mediated inflammation can drive cancer progression. EGCG was further found to decrease protein expression of both HIF-1α and its downstream target vascular endothelial growth factor (VEGF) in MCF-7 cells in a dose-dependent manner [10]. In addition, EGCG was found to protect the cells from ionizing radiation. A recent study showed that, with a simple pretreatment of 50 μM EGCG, human epidermal keratinocytes (HaCaT cell line) were protected from radiation-induced (20 Gy) cytotoxicity [11]. This was demonstrated by a reduction in (1) apoptotic cells as analyzed by flow cytometry of annexin V/propidium iodide double staining, (2) damage to the mitochondria analyzed by MitoTracker Red staining and upregulation of superoxide dismutase 2, (3) total cellular ROS as determined by DCFDA staining, and (4) γH2AX foci, a marker of DNA damage [11]. They also observed an EGCG-dependent transcriptional induction of heme oxygenase-1, which the authors concluded to be the primary source of the protective effect. After treatment with EGCG following either siRNA knockdown or use of a specific inhibitor of heme oxygenase-1, the protective effects diminished [11].

Bottom Line: This paper reviews the biological effects of a group of natural compounds called polyphenols, including apigenin, epigallocatechin gallate, genistein, and (-)-epicatechin, with a focus on the latter. (-)-Epicatechin has several unique features responsible for a variety of its effects.One of these is its ability to interact with and neutralize reactive oxygen species (ROS) in the cell. (-)-Epicatechin also modulates cell signaling including the MAP kinase pathway, which is involved in cell proliferation.This paper discusses the potential of some phenolic compounds to maintain, protect, and possibly reinstate health.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA ; Karmanos Cancer Institute, Detroit, MI 48201, USA.

ABSTRACT
With recent insight into the mechanisms involved in diseases, such as cardiovascular disease, cancer, stroke, neurodegenerative diseases, and diabetes, more efficient modes of treatment are now being assessed. Traditional medicine including the use of natural products is widely practiced around the world, assuming that certain natural products contain the healing properties that may in fact have a preventative role in many of the diseases plaguing the human population. This paper reviews the biological effects of a group of natural compounds called polyphenols, including apigenin, epigallocatechin gallate, genistein, and (-)-epicatechin, with a focus on the latter. (-)-Epicatechin has several unique features responsible for a variety of its effects. One of these is its ability to interact with and neutralize reactive oxygen species (ROS) in the cell. (-)-Epicatechin also modulates cell signaling including the MAP kinase pathway, which is involved in cell proliferation. Mutations in this pathway are often associated with malignancies, and the use of (-)-epicatechin holds promise as a preventative agent and as an adjunct for chemotherapy and radiation therapy to improve outcome. This paper discusses the potential of some phenolic compounds to maintain, protect, and possibly reinstate health.

No MeSH data available.


Related in: MedlinePlus