Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition

Miyamoto, Morikazu; Takano, Masashi; Aoyama, Tadashi; Soyama, Hiroaki; Ishibashi, Hiroki; Kato, K.; Iwahashi, Hideki; Takasaki, Kazuki; Kuwahara, Mika; Matuura, Hiroko; Sakamoto, Takahiro; Yoshikawa, Tomoyuki; Furuya, Kenichi

doi:10.21873/anticanres.12222

Cited by 11 publications

(17 citation statements)

References 23 publications

(33 reference statements)

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“…GO and KEGG analyses indicated that the differentially expressed ARGs were mainly enriched mainly in platinum drug resistance. Studies have shown that the induction of autophagy in cancer can increase cisplatin resistance (25,26), consistent with our results, suggesting that these ARGs can promote the progression of ccRCC through platinum drug resistance. However, further experiments are needed to verify the role of autophagy in ccRCC.…”

Section: Discussionsupporting

confidence: 92%

Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

et al. 2020

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Abnormal autophagy is closely related to the development of cancer. Many studies have demonstrated that autophagy plays an important role in biological function in clear cell renal cell carcinoma (ccRCC). This study aimed to construct a prognostic signature for ccRCC based on autophagy-related genes (ARGs) to predict the prognosis of ccRCC. Differentially expressed ARGs were obtained from ccRCC RNA-seq data in The Cancer Genome Atlas (TCGA) database. ARGs were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The prognostic ARGs used to construct the risk score models for overall survival (OS) and disease-free survival (DFS) were identified by Cox regression analyses. According to the median value of the risk score, patients were divided into a high-risk group and a low-risk group. The OS and DFS were analyzed by the Kaplan-Meier method. The predictive accuracy was determined by a receiver operating characteristic (ROC) curve analysis. Additionally, we performed stratification analyses based on different clinical variables and evaluated the correlation between the risk score and the clinical variables. The differentially expressed ARGs were mainly enriched in the platinum drug resistance pathway. The prognostic signatures based on 11 ARGs for OS and 5 ARGs for DFS were constructed and showed that the survive time was significantly shorter in the high-risk group than in the low-risk group (P < 0.001). The ROC curve for OS exhibited good predictive accuracy, with an area under the curve value of 0.738. In the stratification analyses, the OS time of the high-risk group was shorter than that of the low-risk group stratified by different clinical variables. In conclusion, an autophagy-related signature for OS we constructed can independently predict the prognosis of ccRCC patient, and provide a deep understanding of the potential biological mechanisms of autophagy in ccRCC.

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Section: Discussionsupporting

confidence: 92%

Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

et al. 2020

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“…Hydrochloroquine (HCQ) is a less toxic derivative of CQ with similar clinical applications. HCQ cellular effects are similar to those of CQ and consistently its was shown to possess CPT chemosensitizing properties in vitro [46,47,49]. 33.…”

Section: Chloroquine and Its Derivativesmentioning

confidence: 80%

“…The molecular mechanism of PXD action was suggested to involve X-linked inhibitor of apoptosis protein (XIAP) and FLICE inhibitory protein (FLIP) downregulation as well as direct inhibition of topoisomerase II and ENOX2 (ecto-NOX disulfide-thiol exchanger 2). PXD was shown to sensitize ovarian cancer cell line towards CPT [47,85]. This was accompanied by XIAP downregulation and autophagy inhibition with Beclin-1 inhibition.…”

Section: Phenoxofiolmentioning

confidence: 99%

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Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer

Gąsiorkiewicz

Koczurkiewicz-Adamczyk

Piska

et al. 2020

Invest New Drugs

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Summary Although cisplatin is one of the most common antineoplastic drug, its successful utilisation in cancer treatment is limited by the drug resistance. Multiple attempts have been made to find potential cisplatin chemosensitisers which would overcome cancer cells resistance thus improving antineoplastic efficacy. Autophagy modulation has become an important area of interest regarding the aforementioned topic. Autophagy is a highly conservative cellular self-digestive process implicated in response to multiple environmental stressors. The high basal level of autophagy is a common phenomenon in cisplatin-resistant cancer cells which is thought to grant survival benefit. However current evidence supports the role of autophagy in either promoting or limiting carcinogenesis depending on the context. This encourages the search of substances modulating the process to alleviate cisplatin resistance. Such a strategy encompasses not only simple autophagy inhibition but also harnessing the process to induce autophagy-dependent cell death. In this paper, we briefly describe the mechanism of cisplatin resistance with a special emphasis on autophagy and we give an extensive literature review of potential substances with cisplatin chemosensitising properties related to autophagy modulation.

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“…Conversely, Miyamoto et al reported that phenoxodiol, a synthetic analogue of the plant isoflavone genistein with an improved anticancer efficacy (0.5-2 µg/mL), inhibited autophagy and X-linked inhibitor of apoptosis protein (XIAP), thus sensitizing ovarian clear cell carcinoma cells (KK cells) to cisplatin treatment [191].…”

Section: Isoflavonesmentioning

confidence: 99%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.

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Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition

Abstract: PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment.

Cited by 11 publications

References 23 publications

Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Identification of an Autophagy-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

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