Proteomic Changes Induced by Podophyllotoxin in Human Cervical Carcinoma<font>HeLa</font>Cells

Wang, Bochan; Chen, Lifeng; Zhao, Hong; Zhou, Li; Shi, Ping; Huang, Zhiwei

doi:10.1142/s0192415x13500122

Cited by 11 publications

(9 citation statements)

References 36 publications

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“…In a nutshell, the excellent selective therapeutic effect of PTOX and its derivatives on a variety of tumors has attracted increasing attention. Besides the above mentioned tumors, researchers have further developed more PTOX derivatives against other different cancers as well, including pancreatic cancer ( Pan et al, 2020 ), leukemia ( Zhang et al, 2016b ), head and neck squamous cell carcinoma (HNSCC) ( Resendez et al, 2019 ), cervical carcinoma ( Wang et al, 2013 ), etc.…”

Section: Ptox Derivatives As An Anticancer Drug For Various Cancersmentioning

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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Section: Ptox Derivatives As An Anticancer Drug For Various Cancersmentioning

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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“…This compound and its derivatives have great significance as antineoplastic drugs and antiviral agents due to the biological activities that they exhibit. Podophyllotoxin and its derivatives are currently used in chemotherapy for various cancer types, including cervical carcinoma, osteosarcoma, nasopharyngeal carcinoma, colon cancer, breast cancer, prostate cancer, testicular carcinoma, small cell lung cancer and lymphoma (4–8). However, studies investigating the antitumor effect on GC are limited (9) and the molecular mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis of human gastric cancer SGC-7901 cells induced by podophyllotoxin

Ji¹,

Yu-bin²

2014

Experimental and Therapeutic Medicine

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Numerous studies have demonstrated that podophyllotoxin and its derivatives exhibit antitumor effects. The aim of the present study was to investigate SGC-7901 cell apoptosis and the underlying mechanism induced by podophyllotoxin. SGC-7901 cells were treated with varying concentrations of podophyllotoxin. MTT assays and flow cytometry were used to evaluate the effects of podophyllotoxin on the proliferation and apoptosis of SGC-7901 cells, while fluorescence inverted microscopy was used to observe the morphology of SGC-7901 cells that had been dyed with Hoechst 33258. In addition, laser scanning confocal microscopy was used to analyze the mitochondrial membrane potential (MMP) of SGC-7901 cells dyed with Rhodamine 123. Western blotting was performed to analyze the expression levels of cytochrome c (cyt-c), caspase-9 and caspase-3 in the SGC-7901 cells. The results indicated that podophyllotoxin was capable of inhibiting growth and inducing the apoptosis of SGC-7901 cells in a dose-dependent manner, causing cell cycle arrest at the G2/M phase. After 48 h of treatment, the apoptotic morphology of SGC-7901 cells was clear, exhibiting cell protuberance, concentrated cytoplasms and apoptotic bodies. Following 24 h of treatment, the MMP of the SGC-7901 cells decreased. In addition, after 48 h, the expression of cyt-c was shown to be upregulated, while the expression levels of pro-caspase-9 and pro-caspase-3 in the SGC-7901 cells were shown to be downregulated. In conclusion, apoptosis can be induced in SGC-7901 cells by podophyllotoxin, potentially via a mitochondrial pathway, indicating that podophyllotoxin may be a potent agent for cancer treatment.

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“…7−9 Our group previously found that PPT has higher antitumor activity and a broader antitumor spectrum than its derivatives. 10 Its antineoplastic activities are mainly attributed to preventing the assembly of tubulin into microtubules and inducing apoptosis. 11,12 However, PPT has been abandoned as a possible antitumor agent because of its water insolubility and adverse effects.…”

Section: ■ Introductionmentioning

confidence: 99%

GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

Liu

Zhu

et al. 2017

ACS Appl. Mater. Interfaces

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Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.

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Proteomic Changes Induced by Podophyllotoxin in Human Cervical CarcinomaHeLaCells

Cited by 11 publications

References 36 publications

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Apoptosis of human gastric cancer SGC-7901 cells induced by podophyllotoxin

GSH-Activated NIR Fluorescent Prodrug for Podophyllotoxin Delivery

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