Curcumin Nicotinate Selectively Induces Cancer Cell Apoptosis and Cycle Arrest through a P53-Mediated Mechanism

He, Yingchun; He, Long; Khoshaba, Ramina; Lü, Fang; Cai, Chuan; Zhou, Fangliang; Liao, Duan‐Fang; Cao, Deliang

doi:10.3390/molecules24224179

Cited by 43 publications

(36 citation statements)

References 39 publications

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“…19 Many therapeutic approaches have been developed to regulate the cell cycle in cancers. 20 CDK1 is a catalytic subunit of a protein kinase complex, which induces cell entry into mitosis. This gene is responsible for controlling the transition from G 1 to S phase and from G 2 to M phase of the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

CDK1 serves as a potential prognostic biomarker and target for lung cancer

Zhang

et al. 2020

J Int Med Res

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Objective: Evidence from cell and mouse models and human tissues suggests that cyclin dependent kinase 1 (CDK1) is involved in lung cancer (LC) tumorigenesis. However, the different types of expression patterns and prognostic results of CDK1 need further analysis.Methods: In the current study, we assessed CDK1 expression and LC patient outcomes using data from the Oncomine, GEPIA, and Kaplan-Meier Plotter databases. Additionally, mutations in the CDK1 gene were analyzed by using the cBioPortal database. The expression of CDK1 was verified by real-time quantitative PCR using the Human Protein Atlas database and human tissues. Results: Expression of CDK1 was higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in normal lung samples. Moreover, CDK1 expression was linked to disease progression. Survival analysis indicated that upregulation of CDK1 was related to poor overall survival, low first progression, and post-progression survival in patients with LC. Conclusions: Our results indicate that CDK1 is a potential clinical target and prognostic biomarker for patients with LC.

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Section: Discussionmentioning

confidence: 99%

CDK1 serves as a potential prognostic biomarker and target for lung cancer

Zhang

et al. 2020

J Int Med Res

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“…Therefore, in the present study the increase of cyclin B1 further confirms that a higher proportion of HepG2/ADM cells were in the G 2 /M phase following digitoxin treatment. With respect to decreasing level of p-CDK1 (Thr14), some signaling pathways, which are activated to regulate cell cycle events such as P21 and P53 ( 52 , 53 ) may be responsible for this phenomenon. Similar results have been reported in other studies.…”

Section: Discussionmentioning

confidence: 99%

Digitoxin inhibits proliferation of multidrug‑resistant HepG2 cells through G2/M cell cycle arrest and apoptosis

et al. 2020

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Hepatocellular carcinoma (HCC) remains a challenge in the medical field due to its high malignancy and mortality rates particularly for HCC, which has developed multidrug resistance. Therefore, the identification of efficient chemotherapeutic drugs for multidrug resistant HCC has become an urgent issue. Natural products have always been of significance in drug discovery. In the present study, a cell-based method was used to screen a natural compound library, which consisted of 78 compounds, and the doxorubicin-resistant cancer cell line, HepG2/ADM, as screening tools. The findings of the present study led to the shortlisting of one of the compounds, digitoxin, which displayed an inhibitory effect on HepG2/ADM cells, with 50% inhibitory concentration values of 132.65±3.83, 52.29±6.26, and 9.13±3.67 nM for 24, 48, and 72 h, respectively. Immunofluorescence, western blotting and cell cycle analyses revealed that digitoxin induced G 2 /M cell cycle arrest via the serine/threonine-protein kinase ATR (ATR)-serine/threonine-protein kinase Chk2 (CHK2)-M-phase inducer phosphatase 3 (CDC25C) signaling pathway in HepG2/ADM cells, which may have resulted from a DNA double-stranded break. Digitoxin also induced mitochondrial apoptosis, which was characterized by changes in the interaction between Bcl-2 and Bax, the release of cytochrome c , as well as the activation of the caspase-3 and −9. To the best of our knowledge, the present study is the first report that digitoxin displays an anti-HCC effect on HepG2/ADM cells through G 2 /M cell cycle arrest, which was mediated by the ATR-CHK2-CDC25C signaling pathway and mitochondrial apoptosis. Therefore, digitoxin could be a promising chemotherapeutic agent for the treatment of patients with HCC.

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“…HO-3867 refolded mutant p53 in several cancer cell lines as judged by conformation-specific antibody staining. Although both compounds possess antiproliferative activity, they demonstrated varying degrees of selectivity toward killing cells with mutant p53 (compared to null and WT p53 cell lines), consistent with their action via both p53-dependent and independent routes [84,85,87,88].…”

Section: Alkylating Agentsmentioning

confidence: 70%

Follow the Mutations: Toward Class-Specific, Small-Molecule Reactivation of p53

Loh

2020

Biomolecules

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The mutational landscape of p53 in cancer is unusual among tumor suppressors because most of the alterations are of the missense type and localize to a single domain: the ~220 amino acid DNA-binding domain. Nearly all of these mutations produce the common effect of reducing p53’s ability to interact with DNA and activate transcription. Despite this seemingly simple phenotype, no mutant p53-targeted drugs are available to treat cancer patients. One of the main reasons for this is that the mutations exert their effects via multiple mechanisms—loss of DNA contacts, reduction in zinc-binding affinity, and lowering of thermodynamic stability—each of which involves a distinct type of physical impairment. This review discusses how this knowledge is informing current efforts to develop small molecules that repair these defects and restore function to mutant p53. Categorizing the spectrum of p53 mutations into discrete classes based on their inactivation mechanisms is the initial step toward personalized cancer therapy based on p53 allele status.

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Curcumin Nicotinate Selectively Induces Cancer Cell Apoptosis and Cycle Arrest through a P53-Mediated Mechanism

Cited by 43 publications

References 39 publications

CDK1 serves as a potential prognostic biomarker and target for lung cancer

CDK1 serves as a potential prognostic biomarker and target for lung cancer

Digitoxin inhibits proliferation of multidrug‑resistant HepG2 cells through G2/M cell cycle arrest and apoptosis

Follow the Mutations: Toward Class-Specific, Small-Molecule Reactivation of p53

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