Natural products targeting the ATR-CHK1 signaling pathway in cancer therapy

Ahmed, Salman; Alam, Waqas; Aschner, Michael; Alsharif, Khalaf F.; Albrakati, Ashraf; Saso, Luciano; Khan, Haroon

doi:10.1016/j.biopha.2022.113797

Cited by 11 publications

(7 citation statements)

References 106 publications

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“…The major substrates of Chk1 are Wee1, CDC25A, and CDC25C. Phosphorylation of these proteins leads to functional inhibition of CDK1 and CDK2, which in turn results in temporary suppression of the cell cycle to prevent abnormal cell division and permanent loss of genetic material 29 . Because of the observed involvement of claspin in SFB‐mediated cancer cell apoptosis, we next investigated the expressions of proteins involved in the ATR‐Chk1 signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

“…30 In accordance to our findings, previous studies have shown that natural bioactive compounds can exert anticancer effects by targeting the ATR-Chk1 signaling pathway. 29 A study analyzing bioactive compounds of Curcuma longa has found that curcumin suppresses three major DNA damage response pathways by inhibiting ATR and histone acetyltransferases, which in turn induce mitotic catastrophe and cancer cell death. These events are collectively responsible for curcuminmediated sensitization of cancer cells to PARP inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, these observations indicate that plant‐derived bioactive compounds can be used as adjuvants for anticancer treatments to induce cell cycle arrest at the G2/M phase and cancer cell death. These phytochemicals are particularly effective for targeting chemotherapy‐ and radiotherapy‐resistant cancer cells because of the lack of p53 activity 29 …”

Section: Discussionmentioning

confidence: 99%

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Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and ATR‐Chk1 signaling pathways

Hsieh,

Lin,

et al. 2024

Environmental Toxicology

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The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced‐stage OSCC is associated with poor prognosis and a 5‐year survival rate of only 30%–50%. The present study was designed to investigate the anticancer effect and mode of action of Glycyrrhiza‐derived semilicoisoflavone B (SFB) in 5‐fluorourasil (5FU)‐resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro‐apoptotic mode of action, SFB was found to increase Fas‐associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro‐apoptotic Bim expression and reduce anti‐apoptotic Bcl‐2 and Bcl‐xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB‐mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP‐ribose) polymerase confirmed the induction of caspase‐mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1/2 (ERK) phosphorylation to execute its pro‐apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR‐Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU‐resistant OSCC by modulating mitogen‐activated protein kinase (MAPK) and ATR‐Chk1 signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and ATR‐Chk1 signaling pathways

Hsieh,

Lin,

et al. 2024

Environmental Toxicology

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“…Chemotherapeutic drugs that target replicating DNA cells activate the ATR-CHK1 pathway ( da Costa et al, 2023 ). Additionally, inhibitors of ATR-CHK1 have been reported to decrease the levels of P-gp ( Ahmed et al, 2022 ).…”

Section: The Mechanism Of Mdrmentioning

confidence: 99%

“…Natural products, including curcumin, mangostin, resveratrol, and carnosine, block the G1-S phase but not affect the cell division cycle of proliferating healthy cells. Studies have shown that resveratrol, mangostin, and carnosine are agonists of ATR-CHK1, and kaempferol, curcumin, raffinose, and caffeine are inhibitors of ATR-CHK1, and these phytochemicals may help overcome tumor resistance ( Ahmed et al, 2022 ). PU-1 is a sesquiterpenoid derived from Asteraceae that inhibits the growth of drug-resistant tumor cells through DNA damage, G2/M cell cycle blockade and apoptosis ( Hegazy et al, 2021 ) ( Figure 1 ).…”

Section: The Mechanism Of Mdrmentioning

confidence: 99%

Natural products reverse cancer multidrug resistance

Zou,

Chen,

Luo

et al. 2024

Front. Pharmacol.

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Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

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