&lt;p&gt;Leonurine Promotes Cisplatin Sensitivity in Human Cervical Cancer Cells Through Increasing Apoptosis and Inhibiting Drug-Resistant Proteins&lt;/p&gt;

Lin, Min; Pan, Chunyu; Xu, Wenbin; Li, Jingwei; Zhu, Xueqiong

doi:10.2147/dddt.s252112

Cited by 13 publications

(9 citation statements)

References 34 publications

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“…Our previous study had found that an active ingredient of Yimucao, leonurine, combined with cisplatin exerted synergistic antitumorigenic effects on cervical cancer ( 47 ); however, the detailed mechanism of Yimucao’s actions and its active ingredients’ synergism with cisplatin on cervical cancer is currently unknown. In the present study, we attempted to illustrate the synergistic mechanism of Yimucao and cisplatin by applying a network pharmacology approach.…”

Section: Discussionmentioning

confidence: 99%

Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

et al. 2022

Front. Oncol.

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Yimucao has been used as an herbal medicine to treat gynecological diseases. Common genes of Yimucao active compounds were investigated using network pharmacology. The components and targets of Yimucao were retrieved from the TCMSP database. Cervical cancer targets were collected from GeneCards, TTD, DisGeNET, and KEGG. Cisplatin-related genes were downloaded from GeneWeaver. The protein-protein interaction (PPI) network was created using the STRING database. A drug-bioactive compound-disease-target network was constructed using Cytoscape. GO and KEGG analyses were performed to investigate common targets of quercetin and cisplatin in cervical cancer. We found that quercetin was the highly bioactive compound in Yimucao. The drug-bioactive compound-disease-target network contained 93 nodes and 261 edges. Drug-related key targets were identified, including EGFR, IL6, CASP3, VEGFA, MYC, CCND1, ERBB2, FOS, PPARG, and CASP8. Core targets were primarily related to the response to metal ions, cellular response to xenobiotic stimulus, and transcription factor complex. The KEGG pathway analysis revealed that quercetin and cisplatin may affect cervical cancer through platinum drug resistance and the p53 and HIF-1 pathways. Furthermore, quercetin combined with cisplatin downregulated the expression of EGFR, MYC, CCND1, and ERBB2 proteins and upregulated CASP8 expression in HeLa and SiHa cells. Functionally, quercetin enhanced cisplatin-induced anticancer activity in cervical cancer cells. Our results indicate that quercetin can be used to overcome cisplatin resistance in cervical cancer cells.

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Section: Discussionmentioning

confidence: 99%

Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

et al. 2022

Front. Oncol.

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“…SiHa and C33A cells were lysed in a lysis buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, and 0.5% NP-40) containing protease and phosphatase inhibitors with a Mini tablet (Thermo Fisher, A32961) added to 10 mL of the lysis buffer. The expression of FBXO22, p57 Kip2 , and GAPDH was examined by Western blotting analysis as previously described [ 31 ]. The following primary antibodies were used for Western blotting analysis: mouse anti-FBXO22 (1:500, sc-100736, Santa Cruz), rabbit anti-p57 (1:1000, sc-1040, Santa Cruz), mouse anti-Ub (1:500, sc-166355, Santa Cruz), mouse anti-GAPDH (1:2500, 80602-840, Calbiochem) Image J software was used for the measurement of band density and relative expression of a protein the ratio of its band density normalized by that of its corresponding GAPDH protein band.…”

Section: Methodsmentioning

confidence: 99%

Fbxo22 promotes cervical cancer progression via targeting p57Kip2 for ubiquitination and degradation

et al. 2022

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F-box only protein 22 (FBXO22) is a key subunit of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase complex. Little is known regarding its biological function and underlying molecular mechanisms in regulating cervical cancer (CC) progression. In this study, we aim to explore the role and mechanism of FBXO22 in CC progression. The correlation between FBXO22 and clinicopathological characteristics of CC was analyzed by tissue microarray. MTT, colony formation, flow cytometry, Western blotting, qRT-PCR, protein half-life, co-immunoprecipitation, ubiquitination, and xenograft experiments were performed to assess the functions of FBXO22 and potential molecular mechanisms of FBXO22-mediated malignant progression in CC. The expression of FBXO22 protein in CC tissues was higher than that in adjacent non-tumor cervical tissues. Notably, high expression of FBXO22 was significantly associated with high histology grades, positive lymph node metastasis, and poor outcomes in CC patients. Functionally, ectopic expression of FBXO22 promoted cell viability in vitro and induced tumor growth in vivo, while knockdown of FBXO22 exhibited opposite effects. In addition, overexpression of FBXO22 promoted G1/S phase progression and inhibited apoptosis in CC cells. Mechanistically, FBXO22 physically interacted with the cyclin-dependent kinase inhibitor p57Kip2 and subsequently mediated its ubiquitination and proteasomal degradation leading to tumor progression. FBXO22 protein level was found negatively associated with p57Kip2 protein levels in patient CC samples. FBXO22 promotes CC progression partly through regulating the ubiquitination and proteasomal degradation of p57Kip2. Our study indicates that FBXO22 might be a novel prognostic biomarker and therapeutic target for CC.

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“…CDDP combination therapy has gained increasing attention, aiming to reduce the side effects of CDDP monotherapy [11,12]. Moreover, several low-toxicity natural products can enhance the anticancer effects of platinum-based drugs [13,14].…”

Section: Introductionmentioning

confidence: 99%

Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway

Zheng

Yang²,

Zhai

et al. 2022

Preprint

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Background: Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis. Methods: Cell lines were treated with CDDP, TA, and CDDP+TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the expression of key factors in the ER stress apoptotic pathway was detected using qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated. Results: The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP+TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher. Conclusions: The combination of TA and CDDP may produce synergistic antitumoral effects, mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.

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<p>Leonurine Promotes Cisplatin Sensitivity in Human Cervical Cancer Cells Through Increasing Apoptosis and Inhibiting Drug-Resistant Proteins</p>

Cited by 13 publications

References 34 publications

Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

Fbxo22 promotes cervical cancer progression via targeting p57Kip2 for ubiquitination and degradation

Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway

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