Reactive oxygen species (ROS) in cancer pathogenesis and therapy: An update on the role of ROS in anticancer action of benzophenanthridine alkaloids

Khan, Abdul Quaiyoom; Rashid, Khalid; AlAmodi, Abdulhadi A.; Agha, Maha Victor; Akhtar, Sabah; Hakeem, Ishrat; Raza, Syed Shadab; Uddin, Shahab

doi:10.1016/j.biopha.2021.112142

Cited by 68 publications

(53 citation statements)

References 228 publications

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“…Hydrogen peroxide (H 2 O 2 ) is one of the most important inducers of apoptosis ( Clément et al, 1998 ). Anticancer compounds have been shown to promote apoptosis via ROS production ( Tables 1 , 2 ) in a number of investigations ( Kopustinskiene et al, 2020 ; Perillo et al, 2020 ; Khan et al, 2021 ; Subramaniam et al, 2021 ). For example, in PC-3 (prostate cancer), HepG2 (hepatic cancer), and MCF-7 (breast cancer) cells, the polyphenol resveratrol was found to cause mitochondrial H 2 O 2 buildup by regulating antioxidant enzymes, resulting in apoptosis ( Khan et al, 2013 ).…”

Section: Role Of Reactive Oxygen Species In Cancer Cell Deathmentioning

confidence: 99%

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications

Farhan

Rizvi

2022

Front. Pharmacol.

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Plant derived polyphenolic compounds are considered critical components of human nutrition and have shown chemotherapeutic effects against a number of malignancies. Several studies have confirmed the ability of polyphenols to induce apoptosis and regression of tumours in animal models. However, the mechanism through which polyphenols modulate their malignant cell selective anticancer effects has not been clearly established. While it is believed that the antioxidant properties of these molecules may contribute to lowering the risk of cancer induction by causing oxidative damage to DNA, it could not be held responsible for chemotherapeutic properties and apoptosis induction. It is a well known fact that cellular copper increases within the malignant cell and in serum of patients harboring malignancies. This phenomenon is independent of the cellular origin of malignancies. Based on our own observations and those of others; over the last 30 years our laboratory has shown that cellular copper reacts with plant derived polyphenolic compounds, by a Fenton like reaction, which generates reactive oxygen species and leads to genomic DNA damage. This damage then causes an apoptosis like cell death of malignant cells, while sparing normal cells. This communication reviews our work in this area and lays the basis for understanding how plant derived polyphenols can behave as prooxidants (and not antioxidants) within the microenvironment of a malignancy (elevated copper levels) and gives rationale for their preferential cytotoxicity towards malignant cells.

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Section: Role Of Reactive Oxygen Species In Cancer Cell Deathmentioning

confidence: 99%

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications

Farhan

Rizvi

2022

Front. Pharmacol.

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“…In addition, reactive oxygen species (ROS) were reported to play an important role in maintaining cancer stemness [ 31 ]. Sestrin2 was able to suppress ROS in cancer cells [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Sestrin2 reduces cancer stemness via Wnt/β-catenin signaling in colorectal cancer

Wei

Zheng

et al. 2022

Cancer Cell Int

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Background Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women in China. In previous studies, Sestrin2 was demonstrated to have functions in CRC. However, the relationship between Sestrin2 and cancer stemness has not been reported. Methods and results To investigate the contribution of Sestrin2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas datasets and found that Sestrin2 was downregulated in CRC. Using a lentivirus vector, we verified that Sestrin2 suppressed CRC cell proliferation, migration, and colony formation. Furthermore, sphere formation, flow cytometry, quantitative PCR, and western blot analysis verified the influence of Sestrin2 on cancer stemness, including the expression of cluster of differentiation 44, octamer-binding transcription factor 4, sex-determining region Y-Box 2, CXC chemokine receptor 4, and the Wnt pathway downstream factors β-catenin and c-Myc. Consistently, the Wnt pathway activator BML-284 partially rescued the effects of Sestrin2 on the expression of proteins related to cancer stemness. Furthermore, in a mouse xenoplant model, tumors expressing Sestrin2 were significantly reduced in size with corresponding changes in cancer stemness. Conclusions Collectively, our results suggest that Sestrin2 inhibits CRC cell progression by downregulating the Wnt signaling pathway. Thus, Sestrin2 may be a promising therapeutic target for CRC.

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“…No cell receptors for these alkaloids have been described; hence, their physiological activity depends on their diffusion into cells and chemical reactivity with membranes, nucleic acids, and proteins, and their consequent interference in different biochemical processes. For example, the disruption of membrane electrochemical gradients, caused by inhibition of Na + /K + ATPases, also hampers different signal transduction pathways, including those mediated by mitogen-activating protein kinases (MAPK), reactive oxygen species (ROS), and intracellular calcium, which, in turn, could be involved in cell death and apoptosis pathways [58]. It has been observed that chelerythrine, chelidonine (stylophorin), cordatine, and nitidine induce ROS formation in tumoral cell lines from diverse human tissues, including bladder, breast, glioma, lung, kidney, pancreas, prostate, skin, stomach, and uvea, among others [30,[57][58][59].…”

Section: Medical and Industrial Applications Of Benzophenanthridinesmentioning

confidence: 99%

“…For example, the disruption of membrane electrochemical gradients, caused by inhibition of Na + /K + ATPases, also hampers different signal transduction pathways, including those mediated by mitogen-activating protein kinases (MAPK), reactive oxygen species (ROS), and intracellular calcium, which, in turn, could be involved in cell death and apoptosis pathways [58]. It has been observed that chelerythrine, chelidonine (stylophorin), cordatine, and nitidine induce ROS formation in tumoral cell lines from diverse human tissues, including bladder, breast, glioma, lung, kidney, pancreas, prostate, skin, stomach, and uvea, among others [30,[57][58][59]. ROS accumulation induced by BZD activates different components of the apoptotic transduction pathways, including both caspase-dependent and independent routes [58].…”

Section: Medical and Industrial Applications Of Benzophenanthridinesmentioning

confidence: 99%

An Update of the Sanguinarine and Benzophenanthridine Alkaloids’ Biosynthesis and Their Applications

et al. 2022

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Benzophenanthridines belong to the benzylisoquinolic alkaloids, representing one of the main groups of this class. These alkaloids include over 120 different compounds, mostly in plants from the Fumariaceae, Papaveraceae, and Rutaceae families, which confer chemical protection against pathogens and herbivores. Industrial uses of BZD include the production of environmentally friendly agrochemicals and livestock food supplements. However, although mainly considered toxic compounds, plants bearing them have been used in traditional medicine and their medical applications as antimicrobials, antiprotozoals, and cytotoxic agents have been envisioned. The biosynthetic pathways for some BZD have been established in different species, allowing for the isolation of the genes and enzymes involved. This knowledge has resulted in a better understanding of the process controlling their synthesis and an opening of the gates towards their exploitation by applying modern biotechnological approaches, such as synthetic biology. This review presents the new advances on BDZ biosynthesis and physiological roles. Industrial applications, mainly with pharmacological approaches, are also revised.

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Reactive oxygen species (ROS) in cancer pathogenesis and therapy: An update on the role of ROS in anticancer action of benzophenanthridine alkaloids

Cited by 68 publications

References 228 publications

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications

Sestrin2 reduces cancer stemness via Wnt/β-catenin signaling in colorectal cancer

An Update of the Sanguinarine and Benzophenanthridine Alkaloids’ Biosynthesis and Their Applications

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