WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells

Zhao, Yan; Wang, Wen; Pan, Wenying; Yu, Yunhai; Huang, Wei; Gao, Jiangang; Zhang, Ying; Zhang, Shiqian

doi:10.3892/mmr.2020.11754

Cited by 14 publications

(20 citation statements)

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“…Similar results have been observed in another BLCA study [47], but also in colon, prostate, pancreatic and lung cancers [48,49], and might be related to enhanced TNFα, which induces cell death and decreases viability [50,51]. Proliferation was found to be increased when WWOX gene was methylated in osteosarcoma [52], while apoptosis was potentiated in ovarian carcinoma through caspase-3 and PARP when WWOX was functional [53]. Moreover, the impact of WWOX on proliferation has also been confirmed in bladder cancer [47].…”

Section: Discussionsupporting

confidence: 83%

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

Kołat

Kałuzińska

Płuciennik

2021

Cancers

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The cytogenic locus of the WWOX gene overlaps with the second most active fragile site, FRA16D, which is present at a higher frequency in bladder cancer (BLCA) patients with smoking habit, a known risk factor of this tumor. Recently, we demonstrated the relevance of the role of WWOX in grade 2 BLCA in collaboration with two AP-2 transcription factors whose molecular actions supported or opposed pro-cancerous events, suggesting a distinct character. As further research is needed on higher grades, the aim of the present study was to examine WWOX-AP-2 functionality in grade 3 and 4 BLCA using equivalent in vitro methodology with additional transcriptome profiling of cellular variants. WWOX and AP-2α demonstrated similar anti-cancer functionality in most biological processes with subtle differences in MMP-2/9 regulation; this contradicted that of AP-2γ, whose actions potentiated cancer progression. Simultaneous overexpression of WWOX and AP-2α/AP-2γ revealed that single discrepancies appear in WWOX-AP-2α collaboration but only at the highest BLCA grade; WWOX-AP-2α collaboration was considered anti-cancer. However, WWOX only appeared to have residual activity against oncogenic AP-2γ in grade 3 and 4: variants with either AP-2γ overexpression alone or combined WWOX and AP-2γ overexpression demonstrated similar pro-tumoral behavior. Transcriptome profiling with further gene ontology certified biological processes investigated in vitro and indicated groups of genes consisting of AP-2 targets and molecules worth investigation as biomarkers. In conclusion, tumor suppressor synergism between WWOX and AP-2α is unimpaired in high-grade BLCA compared to intermediate grade, yet the ability of WWOX to guide oncogenic AP-2γ is almost completely lost.

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Section: Discussionsupporting

confidence: 83%

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

Kołat

Kałuzińska

Płuciennik

2021

Cancers

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“…To our knowledge, interplays between cell autophagy and apoptosis participate in the regulation of various diseases, including liver injury [19][20][21], and previous literatures reported that induction of protective autophagy suppresses cell apoptosis to ameliorate liver injury and fibrosis [22][23][24]. In addition, cell autophagy can be modulated by various Chinese medicines, including ASP [26].…”

Section: Discussionmentioning

confidence: 92%

“…Previous data showed that there existed interplays between cell autophagy and death, and activation of protective autophagy was effective to restore cell viability [22][23][24]. Since we had proved that ASP regulated autophagy in the hepatocytes via activating the MEK/ERK pathway, we conjectured that blockage of MEK/ERK pathway was capable of reversing the protective effects of ASP on DBinduced cell death.…”

Section: Sch772984 Abrogated the Protective Effects Of Asp On Db-induced Hepatocyte Deathmentioning

confidence: 91%

“…Given that ASP played an important role in regulating cell autophagy [26], and there existed interplay between autophagy and apoptosis [22][23][24], we conjectured that ASP might regulate autophagy to reverse DB-induced hepatocyte death. To validate this hypothesis, the hepatocytes were treated with ASP and DB for 6 h according to our preliminary experiments (data not shown).…”

Section: Asp Triggered Autophagy To Protect Hepatocytes From Db-induced Cell Deathmentioning

confidence: 99%

“…Interestingly, ASP has been validated as an ideal and effective therapy drug for liver injury [16][17][18], specifically, Cao et al report that ASP suppresses oxidative stress and hepatic apoptosis to attenuate acetaminophen-induced liver injury [16], Wang et al find that ASP regulates the IL-22/STAT3 pathway to alleviate CCl(4)-induced liver fibrosis [18], and Gao et al support that ASP ameliorates hepatic injury in mice models [17]. In addition, interplay of autophagy and apoptosis plays important role in regulating the development of liver injury [19][20][21], and to our knowledge, induction of protective autophagy suppressed cell apoptosis [22][23][24], and DB promotes liver injury by inducing apoptotic cell death [4,25,5] and inactivation of autophagy flux [25]. Of note, ASP is capable of regulating both cell autophagy [26] and apoptosis [15,16], but it is still largely unknown whether ASP can attenuate DB-induced hepatotoxicity via modulating cell autophagy and apoptosis.…”

Section: Introductionmentioning

confidence: 96%

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Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Liu

Zheng

et al. 2021

Bioengineered

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Diosbulbin-B (DB) is a promising therapeutic drug for cancer treatment; however, DB-induced hepatotoxicity seriously limits its clinical utilization. Based on this, the present study investigated whether the Angelica sinensis extract, angelica sinensis polysaccharide (ASP), was effective to attenuate DB-induced cytotoxicity in hepatocytes. The primary hepatocytes were isolated from rats and cultured in vitro, which were subsequently treated with high-dose DB (100 μM) and ASP (12 μg/ml) to establish the DB-induced hepatotoxicity models. MTT assay and flow cytometry (FCM) were performed to evaluate cell viability, and the results showed that high-dose DBinduced cell apoptosis and inhibition of proliferation were reversed by co-treating cells with ASP, which were supported by our Western Blot assay data that ASP upregulated Cyclin D1 and CDK2 to abrogate high-dose DB-induced cell cycle arrest. In addition, ASP exerted its regulating effects on cell autophagy, and we found that ASP increased LC3B-II/I ratio and Atg5, but decreased p62 to activate the autophagy flux. Of note, the MEK/ERK pathway could be activated by ASP in the DB-treated hepatocytes, and the protective effects of ASP on high-dose DB-induced hepatocyte death were abolished by co-treating cells with the autophagy inhibitor (3-methyladenine, 3-MA) and MEK/ERK selective inhibitor (SCH772984). Moreover, blockage of the MEK/ERK pathway suppressed cell autophagy in the hepatocytes co-treated with ASP and high-dose DB. Taken together, this in vitro study illustrated that ASP activated the MEK/ERK pathway mediated autophagy to suppress high-dose DB-induced hepatotoxicity.

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Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity

Mahabady

Mirzaei

Saebfar

et al. 2022

Journal Cellular Physiology

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WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells

Cited by 14 publications

References 0 publications

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity

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