A novel anti-cancer role of β-apopicropodophyllin against non-small cell lung cancer cells

Kim, Ju Yeon; Cho, Jeong-Hyun; Choi, Jong-Ryoo; Shin, Hyun Jin; Song, Jie‐Young; Hwang, Sang‐Gu; Um, Hong Duck; Yoo, Young; Kim, Joon; Park, Jong Kuk

doi:10.1016/j.taap.2018.08.022

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…Epithelial-mesenchymal transition (EMT) is a cellular program that is known to be essential for the development of malignant Kamal et al, 2011bKamal et al, , 2014Sang et al, 2013;Hui et al, 2016;Vishnuvardhan et al, 2017;Zi et al, 2019 Choi et al, 2015a,b;Hong et al, 2016;Zhang et al, 2016bZhang et al, , 2017bKim et al, 2018 tumors. EMT can confer greater initiation and metastatic potential to cancer cells, as well as greater resistance to therapeutic modalities such as chemotherapy (Dongre and Weinberg, 2019).…”

Section: Epithelial-mesenchymal Transition Associated Moleculesmentioning

confidence: 99%

“…These PTOX-based conjugates selectively aggregated in the lung and significantly reduced toxicity to normal organs and gastrointestinal damage compared to VP-16. β-apopicropodophyllin (APP) Compound 9 ( Figure 3 ) also showed potent anticancer activity against NSCLC cells ( Kim et al, 2018 ). Molecularly, APP led to the accumulation of phosphorylated CHK2, p21, and phosphorylated Cdc2, disrupting microtubule polymerization and damaging DNA, and it stimulated the pro-apoptotic ER stress signaling pathway.…”

Section: Ptox Derivatives As An Anticancer Drug For Various Cancersmentioning

confidence: 99%

“…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%

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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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Section: Epithelial-mesenchymal Transition Associated Moleculesmentioning

confidence: 99%

Section: Ptox Derivatives As An Anticancer Drug For Various Cancersmentioning

confidence: 99%

Section: Mechanism Of Ptox Derivatives As An Anticancer Drugmentioning

confidence: 99%

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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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“…Since the last few decades, natural products have always been the focus in the discovery of anti-cancer agents and show significant therapeutic efficacy against many malignancies 14–16. Abietane diterpenes display a wide variety of interesting biological activities, especially anti-proliferative activities against tumor cells 12,17,18.…”

Section: Discussionmentioning

confidence: 99%

<p>14-Deoxycoleon U-induced endoplasmic reticulum stress-mediated apoptosis, autophagy, and cell cycle arrest in lung adenocarcinoma</p>

Peng

et al. 2019

OTT

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Objective 14-Deoxycoleon U is a natural abietane-type diterpene and exerts an inhibitory effect on tumor cells proliferation, which suggests that 14-Deoxycoleon U may be a potent anti-cancerous lead compound for lung cancer treatment. This study was to evaluate potential of 14-Deoxycoleon U to treat lung adenocarcinoma in vitro and in vivo. Methods In the present study, the cell viability and apoptosis morphology of 14-Deoxycoleon U-treated A549 and LLC cells were explored using cell counting kit-8 assay and Hoechst 33258 staining. Then, the protein expressions about apoptosis, endoplasmic reticulum (ER) stress, autophagy and cell cycle were measured using Western blot. The autophagosome formation of 14-Deoxycoleon U-treated A549 cells was visualized using a confocal microscopy. LLC lung adenocarcinoma model was established. Results The results indicated that 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner via caspase-dependent apoptosis. Furthermore, apoptosis of both cells was mediated by 14-Deoxycoleon U-induced ER stress. In addition, 14-Deoxycoleon U-induced A549 and LLC cell autophagy, thus promoting their death. Moreover, 14-Deoxycoleon U-induced cell cycle arrest in both cells via inhibition of cyclin D3, cyclin-dependent kinase 6, CDC2 and up-regulation of p21. In vivo results showed that administration of 14-Deoxycoleon U significantly suppressed LLC growth and adverse effects of 14-Deoxycoleon U on organs might be lower than of adriamycin. Conclusion Overall, our results demonstrated that 14-Deoxycoleon U represses in vitro and in vivo growth of lung adenocarcinoma through ER stress-mediated apoptosis accompanied by autophagy and cell cycle arrest.

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“…[19][20][21]. β-apopicropodophyllin (APP) is a derivative of PPT that disturbs microtubule polymerization and induces apoptosis of NSCLC cells such as NCI-H460, NCI-H1299, A549, and their xenografts in nude mice in vivo models, suggesting that it may be a candidate anti-cancer agent in our previous studies [22,23]. To prove anti-cancer effect of APP extended from these previous findings, anti-cancer or radiosensitizing effect of APP against CRC cells in vitro and in vivo were evaluated in the present study.…”

Section: Introductionmentioning

confidence: 99%

Radiosensitizer Effect of β-Apopicropodophyllin Against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis

Lee¹,

Kwon²,

Kang³

et al. 2021

Preprint

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β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

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A novel anti-cancer role of β-apopicropodophyllin against non-small cell lung cancer cells

Cited by 10 publications

References 37 publications

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

<p>14-Deoxycoleon U-induced endoplasmic reticulum stress-mediated apoptosis, autophagy, and cell cycle arrest in lung adenocarcinoma</p>

Radiosensitizer Effect of β-Apopicropodophyllin Against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis

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