Piceatannol Enhances Cisplatin Sensitivity in Ovarian Cancer via Modulation of p53, X-linked Inhibitor of Apoptosis Protein (XIAP), and Mitochondrial Fission

Farrand, Lee; Byun, Sun‐Sig; Kim, Ji Young; Im-Aram, Akechai; Lee, Jihoon; Lim, Semi; Lee, Ki Won; Suh, Jeong Yong; Lee, Hyong Joo; Tsang, Benjamin K.

doi:10.1074/jbc.m113.487686

Cited by 91 publications

(84 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the pathways in cancer and pathways related to specified cancers (such as prostate and colorectal cancer), 4 pathways including ErbB signaling, focal adhesion, apoptosis and p53 signaling were enriched, suggesting that HNF1B may contribute to drug resistance in ovarian cancer via those pathways. ErbB signaling (91), focal adhesion (92,93), apoptosis (94,95) and p53 signaling (96,97) have been reported to associate with drug resistance in ovarian cancer. For example, miR-21 regulates drug resistance via apoptosis and cellular survival pathways (94), and loss of DOK2 induces carboplatin resistance in ovarian cancer via suppression of apoptosis (98).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Zhang²,

Gao

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Abstract. The expression of HNF1 homeobox B (HNF1B) is associated with cancer risk in several tumors, including ovarian cancer, and its decreased expression play roles in cancer development. However, the study of HNF1B and cancer is limited, and its association with drug resistance in cancer has never been reported. On the basis of array data retrieved from Oncomine and Gene Expression Omnibus (GEO) online database, we found that the mRNA expression of HNF1B in 586 ovarian serous cystadenocarcinomas and in platinum-resistant A2780 epithelial ovarian cancer cells was significantly decreased, indicating a potential role of HNF1B in drug resistance in ovarian cancer. Based on this finding, comprehensive bioinformatics analyses, including protein/ gene interaction, protein-small molecule/chemical interaction, biological process annotation, gene co-occurrence and pathway enrichment analysis and microRNA-mRNA interaction, were performed to illustrate the association of HNF1B with drug resistance in ovarian cancer. We found that among the proteins/ genes, small molecules/chemicals and microRNAs which directly interacted with HNF1B, the majority was associated with drug resistance in cancer, particularly in ovarian cancer. Biological process annotation revealed that HNF1B closely related to 24 biological processes which were all notably associated with ovarian cancer and drug resistance. These results indicated that the downregulation of HNF1B may contribute to drug resistance in ovarian cancer, via its direct interactions with these drug resistance-related proteins/genes, small molecules/chemicals and microRNAs, and via its regulations on the drug resistance-related biological processes. Pathway enrichment analysis of 36 genes which co-occurred with HNF1B, ovarian cancer and drug resistance indicated that the HNF1B may perform its drug resistance-related functions through 4 pathways including ErbB signaling, focal adhesion, apoptosis and p53 signaling. Collectively, in this study, we illustrated for the first time that HNF1B may contribute to drug resistance in ovarian cancer, potentially through the 4 pathways. The present study may pave the way for further investigation of the drug resistance-related functions of HNF1B in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Zhang²,

Gao

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…Notably, the top Mfn1-inhibiting compound identified in this work, piceatannol (Figure 7d), has been confirmed to facilitate Drp1-dependent mitochondrial fission. 29 In this regard, developing selective compounds such as Mfn-targeting inhibitors that control mitochondrial dynamics without affecting basal mitochondrial functions is of great interest, and such compounds could be applied to the treatment of diseases that are accompanied by mitochondrial dysfunction, including neurodegenerative disorders, aging, and cancer.…”

Section: Cell Cycle Arrestmentioning

confidence: 99%

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency

et al. 2015

View full text Add to dashboard Cite

Cell reprogramming technology has allowed the in vitro control of cell fate transition, thus allowing for the generation of highly desired cell types to recapitulate in vivo developmental processes and architectures. However, the precise molecular mechanisms underlying the reprogramming process remain to be defined. Here, we show that depleting p53 and p21, which are barriers to reprogramming, yields a high reprogramming efficiency. Deletion of these factors results in a distinct mitochondrial background with low expression of oxidative phosphorylation subunits and mitochondrial fusion proteins, including mitofusin 1 and 2 (Mfn1/2). Importantly, Mfn1/2 depletion reciprocally inhibits the p53-p21 pathway and promotes both the conversion of somatic cells to a pluripotent state and the maintenance of pluripotency. Mfn1/2 depletion facilitates the glycolytic metabolic transition through the activation of the Ras-Raf and hypoxia-inducible factor 1α (HIF1α) signaling at an early stage of reprogramming. HIF1α is required for increased glycolysis and reprogramming by Mfn1/2 depletion. Taken together, these results demonstrate that Mfn1/2 constitutes a new barrier to reprogramming, and that Mfn1/2 ablation facilitates the induction of pluripotency through the restructuring of mitochondrial dynamics and bioenergetics. Cell Death and Differentiation (2015) 22, 1957-1969 doi:10.1038/cdd.2015; published online 17 April 2015Cell fate transition occurs under various developmental, physiological, and pathological conditions, including normal embryonic development, aging, and tissue regeneration, as well as tumor initiation and progression. Defining the cellular and molecular mechanisms of cell fate transition and learning to control these mechanisms may be essential for treating abnormal pathological conditions resulting from improper regulation of cell fate. The recent development of induced pluripotent stem cell (iPSC) technology has allowed for the reprogramming of somatic cells to pluripotent stem cells through the use of defined pluripotency factors, and has allowed us to more closely mimic and recapitulate the conditions of cell fate transitions.1 In studying aspects of somatic cell reprogramming related to pluripotency, dramatic and complex molecular changes at the genetic, epigenetic, and metabolic levels have been observed during the initial stage of reprogramming.2 Cell reprogramming faces the challenge of balancing stability and plasticity and must overcome critical barriers, such as cell cycle checkpoints, the mesenchymal-epithelial transition, and metabolic reprogramming, to progress cell fate conversion from a stochastic early phase toward pluripotency. 3The p53 pathway limits cell fate transition by inducing classical signaling that leads to cell cycle arrest, senescence, or apoptosis to maintain genome stability in the face of reprogramming-induced stress. Thus, compromising p53 signaling accelerates the reprogramming process.4-6 Recent reports have provided data showing that the fast-cycling population is enric...

show abstract

“…After 24 h of treatment with curcumin or 4-PBA, alone, or in combination, the cells were incubated with Hoechst 33342 (10 mg/ml) for another 15 min at 37 C, and then visualized by the In Cell Analyzer 2000 system. Apoptosis was assessed according to the method of a previous study, 29 based on stereotypic morphological changes, including chromatin condensation, nuclear fragmentation cytoplasmic shrinkage, and the formation of apoptotic bodies (with nuclear fragments). At least 12 fields in each group were observed and at least 400 cells per field were counted.…”

Section: Hoechst 33342 Stainingmentioning

confidence: 99%

Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer

Chen

Wang

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Curcumin and fenretinide are 2 well-known and promising chemotherapeutic compounds via various molecular mechanisms. However, the anticancer capacity of either curcumin or fenretinide is limited. This prompted us to examine the combined anticancer effects of curcumin and fenretinide. Our results demonstrate for the first time that there is synergistic anticancer effect of combined treatment with these 2 agents, leading to enhanced cytotoxicity and enhanced expression level of pro-apoptotic protein cleaved PARP in non-small cell lung cancer (NSCLC) cells while showed little toxicity to rat cardiomyoblast normal cells. The combination treatment was also demonstrated to inhibit lung carcinoma growth in vivo. Furthermore, we show that fenretinide or the ER stress inhibitor 4-PBA decreased curcumin-induced Glucose-regulated protein 78 (GRP78) upregulation, and produced a similar enhanced cytotoxic effect. In addition, GRP78 knockdown by siRNA also enhanced the cytotoxic effect of curcumin in A549 and H1299 cells. Our findings suggest that the 2 small molecules, when used in combination, can potentially be effective therapeutic agents for treating NSCLC, at least in part, by regulating endoplasmic reticulum (ER) chaperone protein GRP78.Abbreviations: NSCLC, non-small cell lung cancer; GRP78, Glucose-regulated protein 78; ER, endoplasmic reticulum; 4-PBA, 4-phenylbutyrate; LLC, Lewis lung carcinoma KEYWORDS Curcumin; fenretinide; GRP78; non-small cell lung cancer

show abstract

Piceatannol Enhances Cisplatin Sensitivity in Ovarian Cancer via Modulation of p53, X-linked Inhibitor of Apoptosis Protein (XIAP), and Mitochondrial Fission

Cited by 91 publications

References 55 publications

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency

Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer

Contact Info

Product

Resources

About