Novel small molecule induces p53-dependent apoptosis in human colon cancer cells

Park, Sang Eun; Min, Yong Ki; Ha, Jae Du; Kim, Bum Tae; Lee, Woo Ghil

doi:10.1016/j.bbrc.2007.04.196

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…A proteína p53 tem sido responsabilizada por uma série de funções regulatórias no desenvolvimento celular, é expressa a partir de um gene regulador chave do ciclo celular que, quando sofre mutações, leva ao desenvolvimento de neoplasias malignas, pois desempenha papel importante nas vias de carcinogênese de diferentes tipos de tecidos, atuando, portanto, como um gene supressor tumoral em condições normais, ou seja, bloqueia a proliferação celular (Park et al, 2007). Em pacientes com neoplasia maligna freqüentemente é visto um polimorfismo, como possível fator prognóstico para o câncer (Hernández Borrero & El-Deiry, 2021;Zhao L, Sanyal, 2022).…”

Section: Introductionunclassified

Análise molecular de ácidos nucléicos a partir de tecidos tumorais prostáticos parafinizados

Silva,

Barros,

Souza

et al. 2023

Braz. J. Hea. Rev.

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As amostras de tecido humano obtidas de procedimentos cirúrgicos são rotineiramente fixadas em formalina e embebidas em parafina para arquivamento em longo prazo, sendo assim, a maioria dos laboratórios possuem grandes arquivos de blocos de parafina. Esses arquivos representam uma importante fonte de material para estudos retrospectivos. O estudo de tecidos parafinizados tem vantagem, por exemplo, sobre os congelados, pois os primeiros preservam uma qualidade morfológica superior e permite análises retrospectivas, além de numerosos, facilmente disponíveis e permitirem, em cortes seriados, a identificação de lesões precursoras de tumores invasivos. O objetivo deste estudo foi otimizar um protocolo de extração do RNA de fragmentos de tecidos tumorais de próstatas, contendo hiperplasia e adenocarcinoma, fixados em formol e conservados em blocos de parafina. Em seguida, a qualidade do RNA extraído foi avaliada mediante a amplificação por PCR do exon 4 do gene TP53, onde se observa um polimorfismo no códon 72 muito relacionado com processos cancerígenos em vários órgãos. Os resultados obtidos demonstraram que foi possível aperfeiçoar um protocolo para detecção do RNA a partir de tecidos tumorais de próstatas parafinizados, sem utilizar inibidores de RNAse usualmente empregados em semelhantes protocolos.

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Section: Introductionunclassified

Análise molecular de ácidos nucléicos a partir de tecidos tumorais prostáticos parafinizados

Silva,

Barros,

Souza

et al. 2023

Braz. J. Hea. Rev.

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“…Hopefully, we may be able to increase the population of functional p53 by stabilizing its folded conformation using a designed compound termed 'chemical chaperon' (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), thereby inducing the apoptosis and cell cycle arrest. Here we tried to design such compounds rationally and to suppress the proliferation of colon cancer HCT116 cells.…”

Section: Introductionmentioning

confidence: 99%

“…The chemical chaperons are expected to stabilize the functional conformation of p53, as in case of other conformational diseases, such as prion diseases (10) or cancer (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) and restore its native conformation. Then, we examined their anti-cancer effects using ex vivo screening, the binding assay using surface plasmon resonance (SPR) and in vivo screening, according to the general flow of rational drug design illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

Novel anti-cancer compounds: Structure-based discovery of chemical chaperons for p53

Okuda

Nakamura²,

Kuwata³

2009

Oncol Rep

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Abstract. Thermal stability of p53 is crucial in preventing cancer proliferation. Critical mutations which significantly destabilize p53 conformation prevent normal interaction between p53 and DNA and consequently interfere with its inhibitory function against cancer proliferation. The purpose of this study was to discover the small compounds called 'chemical chaperons' that can efficiently stabilize the functional p53 conformation and restore the anti-cancer activity. To search for such compounds, we performed a docking simulation using the AutoDock program and the ZINC database. Simply based on the docking energy, we extracted 70 compounds (GJC1-GJC70) and examined their anti-cancer activity using the MTT assay of the human colon cancer cells, HCT116. We found that two compounds, GJC29 and GJC30, significantly inhibited the proliferation of cancer cells compared to the positive control staurosporine. Interaction between p53 and novel anti-cancer compounds were confirmed using SPR measurements. Intriguingly, in the simulated binding mode, both compounds bind to the pocket in the vicinity of the residue V143, one of the mutation hot-spots in p53. Finally, we injected each compound subcutaneously into the nude mice implanted with HCT116 and found that GJC29 has a strong suppressive effect against cancer proliferation in vivo. In conclusion, p53 is an appropriate target for the rational design of the chemical chaperon for cancer treatment.

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Identification of a novel compound (β-sesquiphellandrene) from turmeric (Curcuma longa) with anticancer potential: comparison with curcumin

et al. 2015

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Considering that as many as 80% of the anticancer drugs have their roots in natural products derived from traditional medicine, we examined compounds other than curcumin from turmeric (Curcuma longa) that could exhibit anticancer potential. Present study describes the isolation and characterization of another turmeric-derived compound, β-sesquiphellandrene (SQP) that exhibits anticancer potential comparable to that of curcumin. We isolated several compounds from turmeric, including SQP, α-curcumene, ar-turmerone, α-turmerone, β-turmerone, and γ-turmerone, only SQP was found to have antiproliferative effects comparable to those of curcumin in human leukemia, multiple myeloma, and colorectal cancer cells. While lack of the NF-κB-p65 protein had no effect on the activity of SQP, lung cancer cells that expressed p53 were more susceptible to the cytotoxic effect of SQP than were cells that lacked p53 expression. SQP was also found to be highly effective in suppressing cancer cell colony formation and inducing apoptosis, as shown by assays of intracellular esterase activity, plasma membrane integrity, and cell-cycle phase. SQP was found to induce cytochrome c release and activate caspases that lead to poly ADP ribose polymerase cleavage. SQP exposure was associated with downregulation of cell survival proteins such cFLIP, Bcl-xL, Bcl-2, c-IAP1, and survivin. Furthermore, SQP was found to be synergistic with the chemotherapeutic agents velcade, thalidomide and capecitabine. Overall, our results indicate that SQP has anticancer potential comparable to that of curcumin.

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Novel small molecule induces p53-dependent apoptosis in human colon cancer cells

Cited by 5 publications

References 17 publications

Análise molecular de ácidos nucléicos a partir de tecidos tumorais prostáticos parafinizados

Análise molecular de ácidos nucléicos a partir de tecidos tumorais prostáticos parafinizados

Novel anti-cancer compounds: Structure-based discovery of chemical chaperons for p53

Identification of a novel compound (β-sesquiphellandrene) from turmeric (Curcuma longa) with anticancer potential: comparison with curcumin

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