OAMDP, a novel podophyllotoxin derivative, induces apoptosis, cell cycle arrest and autophagy in hepatoma HepG2 cells

Ren, Jie; Liu, Yü; Li, Lixia; Zhao, Yuexin; Li, Zhongyu; Wu, Chao; Chen, Lin; Hu, Kun

doi:10.1002/cbin.10892

Cited by 14 publications

(16 citation statements)

References 40 publications

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“…In addition, studies have shown that Fipronil can cause a significant increase in the level of ROS in porcine oocytes and severe DNA damage, thereby causing cell apoptosis (Zhou et al, 2019). PPT derivative could induce apoptosis, cell cycle arrest, and autophagy in hepatoma HepG2 cells (Ren et al, 2018). And our results suggested that PPT induced oxidative stress in the embryo, which caused early apoptosis, and the changes in the expression of apoptosis-related genes further confirmed the occurrence of apoptosis.…”

Section: Discussionsupporting

confidence: 67%

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Liao

Wei

et al. 2020

Front. Cell Dev. Biol.

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Podophyllotoxin (PPT) is a kind of lignans extracted from the roots and stems of the genus Podophyllum from the tiller family, and it has been widely used in the treatment of condyloma acuminatum, multiple superficial epithelioma in the clinics. However, PPT has been reported to be toxic and can cause liver defects and other organ poisoning. In addition, emerging evidences also indicate that PPT has reproductive toxicity and causes female reproduction disorders. In this study, we used fertilized oocytes and tried to explore the effects of PPT on the early embryonic development with the mouse model. The results showed that exposure to PPT had negative effects on the cleavage of zygotes. Further analysis indicated that PPT could disrupt the organization of spindle and chromosome arrangement at the metaphase of first cleavage. We also found that PPT exposure to the zygotes induced excessive reactive oxygen species (ROS), suggesting the occurrence of oxidative stress. Moreover, in the PPT-exposed embryos, there was positive γH2A.X and Annexin-V signals, indicating that PPT induced embryonic DNA damage and early apoptosis. In conclusion, our results suggested that PPT could affect spindle formation and chromosome alignment during the first cleavage of mouse embryos, and its exposure induced DNA damage-mediated oxidative stress which eventually led to embryonic apoptosis, indicating the toxic effects of PPT on the early embryo development.

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Section: Discussionsupporting

confidence: 67%

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Liao

Wei

et al. 2020

Front. Cell Dev. Biol.

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“…We thoroughly summarize the effects of PTOX derivatives on different cystatin caspases in cancer cells in the following ( Table 2 ). (i) caspase-3: DPMA ( Sang et al, 2013 ), 4-aza-2,3-didehydropodophyllotoxins ( Kamal et al, 2011b , 2014 ), triazolo linked PTOX conjugates Compound 36 ( Figure 10 ; Vishnuvardhan et al, 2017 ), deoxypodophyllotoxin (DPT) ( Hui et al, 2016 ), biotinylated PTOX derivatives Compound 37 ( Figure 10 ; Zi et al, 2019 ); (ii) caspases-8: hybrids of PTOX and formononetin ( Yang et al, 2019 ); (iii) caspases-9: 4β-amidopodophyllotoxins ( Kamal et al, 2013 ); (iv) caspases−3 and −9: OAMDP Compound 38 ( Figure 10 ; Ren et al, 2018 ) and spin-labeled PTOX derivatives Compound 39 ( Figure 10 ; Yang et al, 2017 ); (v) caspases−3, −8, and −9: β-apopicropodophyllin ( Kim et al, 2018 ), PTOX acetate ( Choi et al, 2015a , b ; Hong et al, 2016 ), aromatic heterocyclic esters of PTOX ( Zhang et al, 2016b ), acid-PTOX conjugate Compound 40 ( Figure 10 ; Zhang et al, 2017b ); (vi) multiple caspases: picropodophyllotoxin Compound 41 ( Figure 10 ; Kwak et al, 2020 ). In addition, PTOX may affect other signaling pathways to trigger cell apoptosis.…”

Section: Mechanism Of Ptox Derivatives As An Anticancer Drugmentioning

confidence: 99%

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Fan

Zhu

Xian

et al. 2021

Front. Cell Dev. Biol.

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Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

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“…In addition, upregulated miRNA-194 may also promote the proliferation and migration of GC cells by activating Wnt signaling by targeting the negative Wnt regulator, SUFU [ 12 ]. Moreover, decreased levels of miR-4317, which targets ZNF322, is related to GC cell proliferation and S-G2/M transition [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Song

et al. 2018

Biol Res

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BackgroundEmerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles.MethodsThe mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA–DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein–protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs.ResultsA set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA–DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results.ConclusionsThe downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.

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OAMDP, a novel podophyllotoxin derivative, induces apoptosis, cell cycle arrest and autophagy in hepatoma HepG2 cells

Cited by 14 publications

References 40 publications

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

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