The effects of bioactive compounds from plant foods on mitochondrial function: A focus on apoptotic mechanisms

doi:10.1016/j.fct.2014.03.017

Food and Chemical Toxicology

Volume 68, June 2014, Pages 154-182

https://doi.org/10.1016/j.fct.2014.03.017 Get rights and content

Highlights

•
Dietary bioactive compounds protect mitochondria against oxidative stress.
•
Natural compounds modulate apoptosis signaling pathways.
•
Food plant compounds lead to mitochondria health/dysfunction in both in vitro and in vivo models.

Abstract

Mitochondria are essential organelles for cellular integrity and functionality maintenance and their imparement is implicated in the development of a wide range of diseases, including metabolic, cardiovascular, degenerative and hyperproliferative pathologies. The identification of different compounds able to interact with mitochondria for therapeutic purposes is currently becoming of primary importance. Indeed, it is well known that foods, particularly those of vegetable origin, present several constituents with beneficial effects on health. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds from plant foods affect mitochondria functionality in healthy and pathological in vitro and in vivo models, paying particular attention to the pathways involved in mitochondrial biogenesis and apoptosis.

Graphical abstract

Section snippets

The mitochondrial kingdom

Mitochondria are the cell main energy producers and are therefore essential for normal cellular functions, including intracellular metabolic activities and signal transduction of various cellular pathways. The predominant physiological function of mitochondria is the generation of adenosine triphosphate (ATP) by oxidative phosphorylation (OXPHOS), but additional functions include the generation and the detoxification of reactive oxygen species (ROS), the involvement in some forms of apoptosis,

Effects of dietary compounds on mitochondrial functionality

The balance of cell proliferation, survival and death normally regulates and maintains homeostasis in multicellular organisms. For these reasons, there is a general interest in identifying natural bioactive compounds that could improve mitochondrial functionality and regulate apoptosis process both in healthy and pathologic conditions. In this context, dietary compounds, mainly those of vegetable origin, have been shown not only to stimulate mitochondrial biogenesis but also to target signaling

Conclusions

Recently research studies have demonstrated that many bioactive compounds present in foods may be used alone or in combination with conventional therapeutic agents to prevent the onset and to control the development of several diseases. The protection of mitochondrial function by these dietary agents may be important in explaining their beneficial effects on health. In this review, the involvement of some dietary compounds in mitochondrial function and dysfunction has been discussed, with

Conflict of Interest

The authors declare that there are no conflicts of interest.

Transparency Document

Acknowledgment

The authors would like to thank to Ms. Monica Glebocki for extensive editing of the manuscript.

References (444)

R.T. Abib et al.
Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage
Food Chem. Toxicol.
(2011)
C.F. Alfredsson et al.
Ellagic acid induces a dose- and time-dependent depolarization of mitochondria and activation of caspase-9 and -3 in human neuroblastoma cells
Biomed. Pharmacother.
(2014)
K.H. Al-Gubory
Mitochondria: omega-3 in the route of mitochondrial reactive oxygen species
Int. J. Biochem. Cell Biol.
(2012)
R. Amodio et al.
Caffeic acid phenethyl ester blocks apoptosis induced by low potassium in cerebellar granule cells
Int. J. Dev. Neurosci.
(2003)
K. Arita et al.
Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids
Biochem. Pharmacol.
(2001)
K. Arita et al.
Mechanisms of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6 polyunsaturated fatty acids
Free Radic. Biol. Med.
(2003)
I.C. Arts et al.
Chocolate as a source of tea flavonoids
Lancet
(1999)
A. Atlante et al.
Genistein and daidzein prevent low potassium-dependent apoptosis of cerebellar granule cells
Biochem. Pharmacol.
(2010)
D. Bagchi et al.
Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice
Gen. Pharmacol.
(1998)
R.S. Balaban et al.
Mitochondria, oxidants, and aging
Cell
(2005)

S.W. Ballinger et al.

Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells

Exp. Eye Res.

(1999)

J.Y. Ban et al.

Catechin and epicatechin from Smilacis chinae rhizome protect cultured rat cortical neurons against amyloid beta protein (25–35)-induced neurotoxicity through inhibition of cytosolic calcium elevation

Life Sci.

(2006)

S. Banerjee et al.

Multi-targeted therapy of cancer by genistein

Cancer Lett.

(2008)

H. Bayir et al.

Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria

Biochim. Biophys. Acta

(2006)

L. Becker et al.

Preprotein translocase of the outer mitochondrial membrane: reconstituted Tom40 forms a characteristic TOM pore

J. Mol. Biol.

(2005)

M. Birringer et al.

Proapoptotic effects of long-chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress

Free Radic. Biol. Med.

(2010)

J.L. Blum et al.

Profiling of fatty acids released during calcium-induced mitochondrial permeability transition in isolated rabbit kidney cortex mitochondria

Toxicol. In Vitro

(2011)

A.M. Bode et al.

Signal transduction pathways: targets for chemoprevention of skin cancer

Lancet Oncol.

(2000)

A.M. Bode et al.

The paradox of arsenic: molecular mechanisms of cell transformation and chemotherapeutic effects

Crit. Rev. Oncol. Hematol.

(2002)

W. Bors et al.

Flavonoids as anti-oxidants: determination of radical-scavenging efficiencies

Methods Enzyol.

(1990)

M. Bouktaib et al.

Regio- and stereoselective synthesis of the major metabolite of quercetin, quercetin-3-O-b-d-glucuronide

Tetrahedron Lett.

(2002)

J. Brenmoehl et al.

Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3

Mitochondrion

(2013)

N. Bushue et al.

Retinoid pathway and cancer therapeutics

Adv. Drug Deliv. Rev.

(2010)

M.C. Carreras et al.

Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease

Mol. Aspects Med.

(2004)

A.O. Çeribaşı et al.

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages

Exp. Toxicol. Pathol.

(2012)

W.C. Chang et al.

Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway

Taiwan J. Obstet. Gynecol.

(2010)

A.M. Chinnaiyan

The apoptosome, heart and soul of the cell death machine

Neoplasia

(1999)

K. Choi et al.

N-acetyl cysteine and caffeic acid phenethyl ester sensitize astrocytoma cells to Fas-mediated cell death in a redox-dependent manner

Cancer Lett.

(2007)

M.J. Chung et al.

Dietary phenolic antioxidants, caffeic acid and Trolox, protect rainbow trout gill cells from nitric oxide-induced apoptosis

Aquat. Toxicol.

(2006)

A. Colquhoun et al.

Gamma-Linolenic acid and eicosapentaenoic acid induce modifications in mitochondrial metabolism, reactive oxygen species generation, lipid peroxidation and apoptosis in Walker 256 rat carcinosarcoma cells

Biochim. Biophys. Acta

(2001)

M.D. Cordero et al.

Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity

Toxicol. Appl. Pharmacol.

(2009)

H.C. Dan et al.

Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP)

J. Biol. Chem.

(2004)

G. de Arriba et al.

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

Toxicol. Appl. Pharmacol.

(2009)

M. Dembowski et al.

Assembly of Tom6 and Tom7 into the TOM core complex of Neurospora crassa

J. Biol. Chem.

(2001)

P.T. Devika et al.

(−)Epigallocatechin-gallate (EGCG) prevents mitochondrial damage in isoproterenol-induced cardiac toxicity in albino Wistar rats: a transmission electron microscopic and in vitro study

Pharmacol. Res.

(2008)

R.A. Dixon et al.

Genistein

Phytochemistry

(2002)

V.M. Adhami et al.

Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo

Clin. Cancer Res.

(2007)

H. Adlercreutz et al.

Phyto-oestrogens and Western diseases

Ann. Med.

(1997)

C. Agarwal et al.

Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release

Carcinogenesis

(2002)

B.B. Aggarwal et al.

Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies

Anticancer Res.

(2004)

C.H. Ahn et al.

Chemosensitizing activity of caffeic acid in multidrug-resistant MCF-7/Dox human breast carcinoma cells

Anticancer Res.

(1997)

A.A. Almeida et al.

Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria

J. Agric. Food Chem.

(2006)

P. Anitha et al.

Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis

Eur. J. Nutr.

(2013)

T. Armeni et al.

Mitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction – two different ways of modulating stress

J. Bioenerg. Biomembr.

(2003)

T.Y. Aw et al.

Nutrient supply and mitochondrial function

Annu. Rev. Nutr.

(1989)

J. Bai et al.

Mitochondrial catalase and oxidative injury

Biol. Signals Recept.

(2001)

S.W. Ballinger et al.

Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells

Circ. Res.

(2000)

S. Banerjee et al.

In vitro and in vivo molecular evidence of genistein action in augmenting the efficacy of cisplatin in pancreatic cancer

Int. J. Cancer

(2007)

V. Bantseev et al.

Mitochondrial “movement” and lens optics following oxidative stress from UV-B irradiation: cultured bovine lenses and human retinal pigment epithelial cells (ARPE-19) as examples

Ann. N. Y. Acad. Sci.

(2006)

S.S. Baroni et al.

Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (type IIb) patients

Free Radic. Res.

(1999)

Cited by (168)

Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology
2024, Endocrine and Metabolic Science
Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology and the role of interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, and metformin. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention for SARS-CoV-2 spike protein related diseases; with broad implications for human health. This review presents the therapeutic possibility of using autophagy to treat spike protein related diseases, and details the interventions to deploy this therapeutic modality.
Plant-derived bioactive compounds in colon cancer treatment: An updated review
2022, Biomedicine and Pharmacotherapy
Citation Excerpt :
Nutrients like sulfur, vitamin B, iron, magnesium, manganese, and cysteine actively modulate mitochondrial enzymes and biogenesis. These phytochemicals protect cells from mitochondrial damage that ultimately prevents the growth of cancer cells [122]. For example, epigallocatechin and genistein affect the pentose phosphate pathway, tricarboxylic acid cycle and lactate production.
Colon cancer is the third most predominant cancer caused by genetic, environmental and nutritional factors. Plant-based compounds are very well known to regress colon cancer in many ways, like delaying tumor growth, managing chemotherapy and radiation therapy side-effects, and working at the molecular levels. Medicinal plants contain many bioactive phytochemicals such as flavonoids, polyphenol compounds, caffeic acid, catechins, saponins, polysaccharides, triterpenoids, alkaloids, glycosides, phenols, quercetin, luteolin, kaempferol and luteolin glycosides, carnosic acid, oleanolic acid, rosmarinic acid, emodin, and eugenol and anthricin. These bioactive compounds can reduce tumor cell proliferation via several mechanisms, such as blocking cell cycle checkpoints and promoting apoptosis through activating initiator and executioner caspase. Traditional medicines have been used globally to treat cancers because of their anti-cancer effects, antioxidant properties, anti-inflammatory properties, anti-mutagenic effects, and anti-angiogenic effects. In addition, these medicines effectively suppress early and intermediate stages of carcinogenesis when administered in their active and pure form. However, traditional medicine is not very popular due to some critical challenges. These include poor solubility and absorption of these compounds, intellectual property-related issues, involvement of drug synergism, absence of drug-likeness, and unsure protocols for their extraction from the plant source. Using bioactive compounds in colon cancer has equal advantages and limitations. This review highlights the benefits and challenges of using bioactive compounds derived from plants for colon cancer. We have also discussed using these compounds to target cancer stem cell self-renewal, its effects on cancer cell metabolism, safety parameters, easy modulation, and their bioavailability.
Melatonin promotes the normal cellular mitochondrial function of lotus seeds through stimulating nitric oxide production
2022, Postharvest Biology and Technology
Citation Excerpt :
Complex II (SDH) couples tightly to complexes I and III in plants, producing a greater impact than complex I alone (Wang et al., 2021a). Ca2+-ATPase acts as a transporter of Ca2+ from cytoplasm to mitochondria (Chaban et al., 2014; Forbes-Hernandez et al., 2014). Consistent levels of these enzymes ensure the efficiency of energy production.
Melatonin (MT) plays a vital role in diverse physiological processes of postharvest fruit and vegetables but information on the involvement of nitric oxide (NO) in the MT pathway is limited. The effect of NO, MT and MT combined with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (MT + cPTIO) on the cellular mitochondrial function of lotus seeds was investigated. The browning of lotus seeds was delayed by NO and MT treatments but aggravated by cPTIO treatment. Reactive oxygen species in the mitochondria of NO and MT-treated seeds were efficiently scavenged by antioxidant enzymes stimulated by the treatment, thus inhibiting malondialdehyde production and oxidative damage of the mitochondria. The activities of energy metabolism-related enzymes involved in the respiratory chain were also increased by NO and MT treatments, thereby enhancing ATP production in the lotus seeds. This resulted in increased mitochondrial membrane potential and oxygen consumption during respiratory metabolism. However, the MT + cPTIO treatment produced the opposite effect to MT alone that increased NOS activity but showed no consistent effect on NR activity. These findings suggested that exogenous MT treatment maintained normal mitochondrial function in lotus seeds by inducing endogenous NO production, which could be resulted from the increased NOS activity.
Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology
2022, Free Radical Biology and Medicine
The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its “dark side” role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer.
Antioxidants effects in health: The bright and the dark sides
2022, Antioxidants Effects in Health: The Bright and the Dark Side
As a double-edge knife, oxidative stress (OS) has shown paradoxical behaviors toward beneficial/harmful responses on human health. In this regard, while the high levels and long-lasting exposure to OS is associated with disease development, low/moderate levels of OS could be a natural defense system in the human body. From the mechanistic point, resilience pathways and related signaling mediators (e.g., Nrf2, catalase, glutathione, heme oxygenase, etc.) are responsible for the final outcome of OS which could be modulated by enzymatic and nonenzymatic approaches. Additionally, natural compounds are promising compounds in modulating OS. Altogether, providing a balance between OS and antioxidants could be a critical step forward in a healthy system.
Brazilian sunberry (Solanum oocarpum Sendtn): Alkaloid composition and improvement of mitochondrial functionality and insulin secretion of INS-1E cells
2021, Food Research International
Chronic high-glucose levels induce the generation of reactive oxygen species leading to mitochondrial dysfunction, which is one of the pathological triggers in the development of diabetes. This study investigated the alkaloid composition of two fruits of the genus Solanum, fruta-do-lobo (Solanum lycocarpum) and juá-açu (Solanum oocarpum), and their capacity to protect against oxidative damage and defective insulin secretion induced by chronic high-glucose levels. LC-MS and molecular network of fruit crude extracts reveals that juá-açu and fruta-do-lobo contain kukoamines and glycoalkaloids, respectively. Two purification processes were used to enrich those alkaloids. Fruta-do-lobo extract rich in glycoalkaloids showed a strong cytotoxicity effect, however the juá-açu enriched extract was able to protect mitochondrial functionality against glucotoxicity and stimulate insulin secretion even under conditions of hyperglycemia. These results are promising and suggest that juá-açu is a potential source of bioactive compounds for adjuvant/co-adjuvant therapy for diabetes.

View all citing articles on Scopus

View full text

Invited ReviewThe effects of bioactive compounds from plant foods on mitochondrial function: A focus on apoptotic mechanisms

Highlights

Abstract

Graphical abstract

Section snippets

The mitochondrial kingdom

Effects of dietary compounds on mitochondrial functionality

Conclusions

Conflict of Interest

Transparency Document

Acknowledgment

Food Chem. Toxicol.

Biomed. Pharmacother.

Int. J. Biochem. Cell Biol.

Int. J. Dev. Neurosci.

Biochem. Pharmacol.

Free Radic. Biol. Med.

Lancet

Biochem. Pharmacol.

Gen. Pharmacol.

Cell

Exp. Eye Res.

Life Sci.

Cancer Lett.

Biochim. Biophys. Acta

J. Mol. Biol.

Free Radic. Biol. Med.

Toxicol. In Vitro

Lancet Oncol.

Crit. Rev. Oncol. Hematol.

Methods Enzyol.

Tetrahedron Lett.

Mitochondrion

Adv. Drug Deliv. Rev.

Mol. Aspects Med.

Exp. Toxicol. Pathol.

Taiwan J. Obstet. Gynecol.

Neoplasia

Cancer Lett.

Aquat. Toxicol.

Biochim. Biophys. Acta

Toxicol. Appl. Pharmacol.

J. Biol. Chem.

Toxicol. Appl. Pharmacol.

J. Biol. Chem.

Pharmacol. Res.

Phytochemistry

Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo

Clin. Cancer Res.

Phyto-oestrogens and Western diseases

Ann. Med.

Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release

Carcinogenesis

Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies

Anticancer Res.

Chemosensitizing activity of caffeic acid in multidrug-resistant MCF-7/Dox human breast carcinoma cells

Anticancer Res.

Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria

J. Agric. Food Chem.

Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis

Eur. J. Nutr.

Mitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction – two different ways of modulating stress

J. Bioenerg. Biomembr.

Nutrient supply and mitochondrial function

Annu. Rev. Nutr.

Mitochondrial catalase and oxidative injury

Biol. Signals Recept.

Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells

Circ. Res.

In vitro and in vivo molecular evidence of genistein action in augmenting the efficacy of cisplatin in pancreatic cancer

Int. J. Cancer

Mitochondrial “movement” and lens optics following oxidative stress from UV-B irradiation: cultured bovine lenses and human retinal pigment epithelial cells (ARPE-19) as examples

Ann. N. Y. Acad. Sci.

Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (type IIb) patients

Free Radic. Res.

Invited Review
The effects of bioactive compounds from plant foods on mitochondrial function: A focus on apoptotic mechanisms