Polyphenols enhance the activity of alkylating agents in leukaemia cell lines

Mahbub, Amani A.; Maitre, Christine L. Le; Haywood-Small, Sarah; Cross, Neil; Jordan-Mahy, Nicola

doi:10.18632/oncotarget.27068

Cited by 18 publications

(29 citation statements)

References 38 publications

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“…Furthermore, the cell cycle in myeloid cells was arrested in G2/M and/or S phase when apigenin was co-administrated with CYCLO. Combined treatment by apigenin and CYCLO increased in γH2AX foci in all examined cell lines, showing DNA damage owing to the apoptosis by this co-therapy [92].…”

Section: Secondary Acute Myeloid Leukemiamentioning

confidence: 84%

“…Many adverse effects such as nausea, vomiting, hair loss, nephrotoxicity, and immune-weakness are associated with CLB therapy in leukemia patients. To reduce CLB side effects, Mahbub et al, disclosed a synergistic reduction in ATP and GSH levels, an increase in cell cycle arrest (in G2/M and/or S phases), DNA damage (an increase in γH2AX foci), and apoptosis (through activation of caspase pathways) in human lymphoid and myeloid leukemia cells by the combination therapy of apigenin with CLB [92].…”

Section: Chlorambucil (Clb)mentioning

confidence: 99%

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Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

et al. 2021

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Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

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Section: Secondary Acute Myeloid Leukemiamentioning

confidence: 84%

Section: Chlorambucil (Clb)mentioning

confidence: 99%

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

et al. 2021

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“…For instance, 4,4

-DHS ( trans -4,4

-dihydroxystilbene) was proven to have antitumor and anti-metastatic effects as it inhibits cell proliferation by arresting the cell cycle at the G1/S phase [ 59 ]. Quercetin and myricetin, two well-known cancer therapeutic agents/autophagy mediators, prevent tumor proliferation by inducing cell cycle arrest and inhibit DNA and/or RNA polymerases of viruses or other microorganisms [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. M8 (3,3

,4,4

,5,5

-hexahydroxystilbene) has been shown to inhibit DNA polymerase and arrest the cell cycle [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes

Hsieh

et al. 2020

Biomolecules

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Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins.

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“…This was associated with a synergistic depletion in GSH levels and DNA damage in lymphoid (CCRF-CEM and Jurkat) cell lines. Although only quercetin and apigenin showed synergistic actions with these chemotherapy agents in myeloid (THP-1 and KG-1a) cell lines [ 24 , 71 ]. However importantly, when these polyphenols were used alone, there was an increase in DNA damage and an induction of apoptosis in all lymphoid and myeloid leukaemia cell lines tested [ 23 , 244 ].…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

“…Polyphenols (quercetin, apigenin, emodin and rhein) also have been shown to synergistically reduce ATP levels (as a marker of cell viability) when combined with alkylating agents (chlorambucil, cisplatin and cyclophosphamide) [ 71 ], antimetabolite agents (methotrexate, 6-mercaptopurine and 5-fluorouracil) [ 23 ] and topoisomerase II inhibitors (doxorubicin and etoposide) in Jurkat, CCRF-CEM and THP-1 cells [ 24 ]. However, in some cell lines, some antagonistic effects were observed when some of these polyphenols were used with some chemotherapy agents, thus care must be taken when selecting the appropriate combination therapies for each leukaemia type [ 23 , 24 ].…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

Alaswad

Mahbub

Maitre

et al. 2021

IJMS

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Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Plant-derived polyphenols have been identified as potent anti-cancer agents and have been shown to work synergistically with standard chemotherapy agents in leukaemia cell lines. Polyphenols have multiple mechanisms of action and have been reported to decrease cell proliferation, arrest cell cycle and induce apoptosis via the activation of caspase (3, 8 and 9); the loss of mitochondrial membrane potential and the release of cytochrome c. Polyphenols have been shown to suppress activation of transcription factors, including NF-kB and STAT3. Furthermore, polyphenols have pro-oxidant properties, with increasing evidence that polyphenols inhibit the antioxidant activity of glutathione, causing oxidative DNA damage. Polyphenols also induce autophagy-driven cancer cell death and regulate multidrug resistance proteins, and thus may be able to reverse resistance to chemotherapy agents. This review examines the molecular mechanism of action of polyphenols and discusses their potential therapeutic targets. Here, we discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism are essential to evaluate their clinical use.

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Polyphenols enhance the activity of alkylating agents in leukaemia cell lines

Cited by 18 publications

References 38 publications

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes

Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

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