A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Reis, Flávio; Monteiro, Filipe Almeida; Nunes, Cláudia; Reis, Filipa S.; Bosco, Bartolomeo; Piazza, Silvano; Domingues, Lucı́lia; Chlapek, Petr; Vlček, Petr; Fabián, Pavel; Rajado, Ana Teresa; Carvalho, Alexandra; Veselská, Renata; Inga, Alberto; Melo, Teresa M. V. D. Pinho e

doi:10.1016/j.celrep.2021.108982

Cited by 28 publications

(20 citation statements)

References 69 publications

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“…Xenograft tumor detection was performed as described . In brief, 1 × 10 6 HT-29 cells were inoculated in the dorsal subcutaneous layer of mice.…”

Section: Materials and Methodsmentioning

confidence: 78%

“…We fasted the rats for 24 h before use (without restriction of water intake). Specific parameters were determined as described in ref .…”

Section: Materials and Methodsmentioning

confidence: 86%

“…Antibodies were as follows: p-STING (1:1000, Abcam Technology, U.K.), p-IRF3 (1:2000, Abcam Technology, U.K.), p-TBK1 (1:1000, Abcam Technology, U.K.), p53 (1:1000, Wuhan Servicebio Technology Co., LTD, China), anti-β-actin (1:1000, Abcam Technology, U.K.), and anti-GAPDH (1:1000, Abcam Technology, U.K.). For specific operation methods, refer to the previous description . The results were calculated by the gray value.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…Xenograft tumor detection was performed as described. 23 In brief, 1 × 10 6 HT-29 cells were inoculated in the dorsal subcutaneous layer of mice. When the tumor volume reached about 100 mm 3 , treatment was started intraperitoneally with SA, HK, or PBS twice a week for 3 weeks.…”

Section: Methodsmentioning

confidence: 99%

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Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer

Wang

et al. 2022

ACS Appl. Mater. Interfaces

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Nanomedicine, constructed from therapeutics, presents an advantage in drug delivery for cancer therapies. However, nanocarrier-based treatment systems have problems such as interbatch variability, multicomponent complexity, poor drug delivery, and carrier-related toxicity. To solve these issues, the natural molecule honokiol (HK), an anticancer agent in a phase I clinical trial (CTR20170822), was used to form a self-assembly nanoparticle (SA) through hydrogen bonding and hydrophobicity. The preparation of SA needs no molecular precursors or excipients in aqueous solution, and 100% drug-loaded SA exhibited superior tumor-targeting ability due to the enhanced permeability and retention (EPR) effect. Moreover, SA significantly enhanced the antitumor immunity relative to free HK, and the mechanism has notable selectivity to the p53 pathway. Furthermore, SA exhibited excellent physiological stability and inappreciable toxicity. Taken together, this supramolecular self-assembly strategy provides a safe and "molecular economy" model for rational design of clinical therapies and is expected to promote targeted therapy of HK, especially in colorectal cancer patients with obvious p53 status.

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“…Xenograft tumor detection was performed as described . In brief, 1 × 10 6 HT-29 cells were inoculated in the dorsal subcutaneous layer of mice.…”

Section: Materials and Methodsmentioning

confidence: 78%

“…We fasted the rats for 24 h before use (without restriction of water intake). Specific parameters were determined as described in ref .…”

Section: Materials and Methodsmentioning

confidence: 86%

Section: Materials and Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer

Wang

et al. 2022

ACS Appl. Mater. Interfaces

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“…There are also several p53 activators that can directly bind to mutant p53 to convert it into a wild-type like structure [ 154 , 155 , 156 ]. These drugs directly reactivate and change p53 activity.…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

P63 and P73 Activation in Cancers with p53 Mutation

et al. 2022

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The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

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Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

Basha,

Mohan

2024

ChemistrySelect

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Transcription factor p53, also known as tumor suppressor protein. Encoded by the TP53 gene, the guardian of genome p53 regulates many gene pathways. Nevertheless, the molecular mechanisms of p53 functioning have been known for a few decades, and the exact role of p53 in cancer therapy is unclear. Also, comprehensive literature on heterocycles as p53‐MDM2 protein‐protein interaction inhibitors is limited. This review covers the molecular mechanism for the p53‐MDM2 interaction and its inhibition by the heterocyclic small molecules. We hope the present comprehensive study will help to develop heterocycles as anticancer drugs that induce apoptosis in tumor cells.

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A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Cited by 28 publications

References 69 publications

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer

P63 and P73 Activation in Cancers with p53 Mutation

Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

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