Antioxidant and anticancer potentials of edible flowers: where do we stand?

Fakhri, Sajad; Tomaş, Merve; Capanoglu, Esra; Hussain, Yaseen; Abbaszadeh, Fatemeh; Lu, Baiyi; Wu, Jian‐Lin; Zou, Liang; Smeriglio, Antonella; Simal-Gándara, Jesús; Cao, Hui; Xiao, Jianbo; Khan, Haroon

doi:10.1080/10408398.2021.1931022

Cited by 20 publications

(22 citation statements)

References 435 publications

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“…It is well known that ROS play critical roles as secondary messengers in several redox-sensitive intracellular signaling pathways. In particular, as an intrinsic apoptosis inducer, ROS act as major regulators of apoptosis by regulating the expression of Bcl-2 family proteins and the activity of MAPK family members and their downstream transcription factors [ 22 , 23 ]. One previous study reported that activation of p38 was an important determinant of IALT-induced apoptosis in pancreatic carcinoma cells [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, while adequate levels of reactive oxygen species (ROS) play an important role as intracellular signaling molecules under normal conditions, their abnormal accumulation induces oxidative stress in cells and promotes apoptosis [ 20 , 21 ]. Moreover, many earlier studies demonstrated that the activation of the MAPK signaling pathway was associated with excessive ROS production [ 22 , 23 , 24 ]. These observations suggest that blocking MAPK signaling while promoting ROS production may be a potential approach for inducing apoptosis in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

Kim

Lee

et al. 2021

Pharmaceutics

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Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to investigate the anti-proliferative effects of IALT in human hepatocellular carcinoma (HCC) cells and to evaluate the potential anti-cancer mechanisms. Our results demonstrated that IALT treatment concentration-dependently suppressed the cell survival of HCC Hep3B cells, which was associated with the induction of apoptosis. IALT increased the expression of death-receptor-related proteins, activated caspases, and induced Bid truncation, subsequently leading to cleavage of poly (ADP-ribose) polymerase. In addition, IALT contributed to the cytosolic release of cytochrome c by destroying mitochondrial integrity, following an increase in the Bax/Bcl-2 expression ratio. However, IALT-mediated growth inhibition and apoptosis were significantly attenuated in the presence of a pan-caspase inhibitor, suggesting that IALT induced caspase-dependent apoptosis in Hep3B cells. Moreover, IALT activated the mitogen-activated protein kinases signaling pathway, and the anti-cancer effect of IALT was significantly diminished in the presence of a potent c-Jun N-terminal kinase (JNK) inhibitor. IALT also improved the generation of intracellular reactive oxygen species (ROS), whereas the ROS inhibitor significantly abrogated IALT-induced growth reduction, apoptosis, and JNK activation. Furthermore, ROS-dependent apoptosis was revealed as a mechanism involved in the anti-cancer activity of IALT in a 3D multicellular tumor spheroid model of Hep3B cells. Taken together, our findings indicate that IALT exhibited anti-cancer activity in HCC Hep3B cells by inducing ROS-dependent activation of the JNK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

Kim

Lee

et al. 2021

Pharmaceutics

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“…In regard to the initiator caspases, CD95 (APO-1/Fas) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are members of the TNF receptor superfamily of death receptors which recruits caspase-8, forming a multimeric complex at the plasma membrane that subsequently activates caspase-3. Caspase-8 causes the release of cytochrome c by increasing the permeability of the outer mitochondrial membrane through cleavage of Bid, a BH3-only protein, and translocation to the mitochondria ( 31 , 32 ). Mitochondrial apoptosis-induced channel (MAC) also increases the release of cytochrome c, which activates caspase-3 through the creation of pro-caspase-9, apoptotic protease activating factor 1 (Apaf-1), and the apoptosome.…”

Section: Resistance Mechanisms In Cancer Chemotherapymentioning

confidence: 99%

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

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“…Antioxidant activity is the primary aspect to evaluate the ability of edible flowers or their extracts to limit or inhibit oxidation. DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2′-Azinobis [3ethylbenzothiazoline-6-sulfonic acid]-diammonium salt), oxygen radi- (Fakhri et al, 2021). The antioxidant and antibacterial effects of flower components are usually combined; they not only act as food protective agents, but also prevent the occurrence of chronic diseases.…”

Section: Edible Flower Sources and Antioxidant Activity In The Medite...mentioning

confidence: 99%

Contribution of edible flowers to the Mediterranean diet: Phytonutrients, bioactivity evaluation and applications

et al. 2022

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The Mediterranean diet is acknowledged to be the healthiest dietary pattern around the world, mainly based on plant foods from the rich Mediterranean flora. It is also known to increase longevity and have positive effects on chronic diseases. This review aimed to investigate the knowledge about the use and consumption of edible flowers as part of the Mediterranean cuisine, based on ethnobotanical and ethnopharmacological studies especially from the last 10 years, and highlight their uses as a nutritious and functional food. In this review, a total of 32 edible flower species used in the Mediterranean diet were listed with their phytochemical composition, edible applications, bioactive properties, and dose, highlighting their nutritional contribution to the Mediterranean diet as well as their health effects. Edible flowers are consumed and widely contribute to the health-promoting properties of the Mediterranean diet through being good sources of macro and micronutrients that enhance the nutritive value of Mediterranean dishes and foods, as well as providing more phytonutrients. Based on this, Mediterranean dishes have the remarkable characteristics of being conducive to mitochondrial health and anti-metabolic diseases. The functional components in edible flowers are clarified here, which might be considered as a new factor for rational diet, natural product development, and medical improvement.

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Antioxidant and anticancer potentials of edible flowers: where do we stand?

Cited by 20 publications

References 435 publications

Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

Contribution of edible flowers to the Mediterranean diet: Phytonutrients, bioactivity evaluation and applications

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