Novel multi-substituted benzyl acridone derivatives as survivin inhibitors for hepatocellular carcinoma treatment

Zhang, Bin; Wang, Ning; Zhang, Cunlong; Gao, Chunmei; Zhang, Wei; Chen, Kang; Wu, Weibin; Chen, Yu Zong; Tan, Chunyan; Liu, Feng; Jiang, Yuyang

doi:10.1016/j.ejmech.2017.02.027

Cited by 38 publications

(15 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among them, a multi-substituted benzyl acridone derivative 8u had good activity against human liver carcinoma HepG2 cells and showed low toxicity in vitr o. Moreover, in vivo preliminary experiments showed that 8u might be a good lead compound in the treatment of HCC 26 . The results showed that 8u might have an anti-proliferative effect against human cancer cells through the induction of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

Wang

Chen

Zhang

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

8u, an acridine derivative, has been proved effective anti-hepatocarcinoma effect, while the underlying mechanism remains unclear. Here, metabolomics and proteomics approaches were applied to study its anti-cancer mechanism and explore its effect on HepG2 cells’ invasion and metastasis abilities. The results showed that 8u significantly suppressed HepG2 cells migration and enhanced cell-to-cell junctions. The inhibition effect of 8u on invasion and metastasis disappeared after HSP90α gene silencing, and was reversed after HSP90α overexpression. The biological experimental results indicated that 8u also blocked PI3K/Akt pathway, thereby reducing fatty acid synthase (FASN) protein expression and disordering intracellular lipid metabolism to inhibit cell invasion and metastasis. In addition, HSP90α protein and PI3K/Akt pathway could co-adjust to each other. These findings demonstrated that 8u could efficiently suppress the invasion and metastasis of HepG2 cells by decreasing the expression of HSP90α protein and inhibiting the PI3K/Akt signaling pathway, which could be used as a potential candidate for the treatment of HCC.

show abstract

Section: Introductionmentioning

confidence: 99%

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

Wang

Chen

Zhang

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…31,32 YM155, an inhibitor of Survivin, could induce autophagy-dependent apoptosis of cancer cells and could be a candidate drug of HCC. 33,34 BIRC5 is also involved in drugs resistance. Melatonin could overcome drug resistance in HCC cells by suppressing Survivin via the COX-2/PI3K/AKT pathway.…”

mentioning

confidence: 99%

<p>Competing Endogenous RNA (ceRNA) Network Analysis of Autophagy-Related Genes in Hepatocellular Carcinoma</p>

Yang

Xue

Xie

et al. 2020

PGPM

View full text Add to dashboard Cite

Autophagy plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). We aimed to develop an autophagy-related genes signature predicting the prognosis of HCC and to depict a competing endogenous RNA (ceRNA) network. Methods: Differentially expressed autophagy-related genes (DE-ATGs), miRNAs and lncRNAs and clinical data of HCC patients were extracted from TCGA. The GO and KEGG analysis were performed to investigate the gene function. Univariate and multivariate Cox regression analysis were used to identify a prognostic signature with the DE-ATGs. And a nomogram, adapted to the clinical characteristics, was established. Then, we established a ceRNA network related to autophagy genes. Results: We screened out 27 differentially expressed genes which were enriched in GO and KEGG pathways related to autophagy and cancers. In univariate and multivariate Cox regression analysis, BIRC5, HSPB8, and SQSTM1 were screened out to establish a prognostic risk score model (AUC=0.749, p<0.01). Kaplan-Meier survival analysis showed that the overall survival of high-risk patients was significantly worse. Furthermore, the signature was validated in the other two independent databases. The nomogram, including the autophagy-related risk signature, gender, stage and TNM, was constructed and validated (C-index=0.736). Finally, the ceRNA network was established based on DE-ATGs, differentially expressed miRNAs and lncRNAs. Conclusion: We constructed a reliable prognostic model of HCC with autophagy-related genes and depicted a ceRNA network of DE-ATGs in HCC which provides a basis for the study of post-transcriptional modification and regulation of autophagy-related genes in HCC.

show abstract

“…Similar to the polysubstituted acridine derivatives, the multisubstituted acridione derivatives are also highly efficient, highly selective G4‐DNA stabilizers . In 2017, Zhang et al reported a new series of multisubstituted benzyl acridone derivatives ( 60 ).…”

Section: G‐quadruplex Stabilizermentioning

confidence: 99%

Therapeutic strategies for targeting telomerase in cancer

Chen

Tang

Shi

et al. 2019

Medicinal Research Reviews

View full text Add to dashboard Cite

Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

show abstract

Novel multi-substituted benzyl acridone derivatives as survivin inhibitors for hepatocellular carcinoma treatment

Cited by 38 publications

References 44 publications

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

<p>Competing Endogenous RNA (ceRNA) Network Analysis of Autophagy-Related Genes in Hepatocellular Carcinoma</p>

Therapeutic strategies for targeting telomerase in cancer

Contact Info

Product

Resources

About