Pharmaceutical and pharmacological approaches for bioavailability enhancement of etoposide

Najar, Ishtiyaq Ahmad; Johri, R.K.

doi:10.1007/s12038-013-9399-3

Cited by 28 publications

(13 citation statements)

References 48 publications

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“…Removal of the glycoside group from the compound’s structure does not significantly affect the etoposide-induced DNA cleavage process and substituting it with, for example, a spermine fragment (as in the case of the mentioned below compound - F14512) significantly increases the potency of the parent compound 136 . Etoposide is used for the treatment of SCLCs, lymphomas (including non-Hodgkin’s lymphomas), acute myeloid leukaemia (AML), testicular and ovarian cancer 123 , 137 , 138 .…”

Section: Topoisomerase Inhibitorsmentioning

confidence: 99%

DNA topoisomerases as molecular targets for anticancer drugs

Buzun

Bielawska

Bielawski

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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The significant role of topoisomerases in the control of DNA chain topology has been confirmed in numerous research conducted worldwide. The prevalence of these enzymes, as well as the key importance of topoisomerase in the proper functioning of cells, have made them the target of many scientific studies conducted all over the world. This article is a comprehensive review of knowledge about topoisomerases and their inhibitors collected over the years. Studies on the structure-activity relationship and molecular docking are one of the key elements driving drug development. In addition to information on molecular targets, this article contains details on the structure-activity relationship of described classes of compounds. Moreover, the work also includes details about the structure of the compounds that drive the mode of action of topoisomerase inhibitors. Finally, selected topoisomerases inhibitors at the stage of clinical trials and their potential application in the chemotherapy of various cancers are described.

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Section: Topoisomerase Inhibitorsmentioning

confidence: 99%

DNA topoisomerases as molecular targets for anticancer drugs

Buzun

Bielawska

Bielawski

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Podophyllotoxin does not cause cell DNA fragmentation and inhibits microtubule assembly in vitro (Loike and Horwitz, 1976b). Related research shows that the semi-derivatives of podophyllotoxin combined with other drugs are widely used in the clinical treatment of small cell lung cancer and lymphoma (Najar and Johri, 2014). At present, there are few studies on breast cancer with podophyllotoxin.…”

Section: Discussionmentioning

confidence: 99%

Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer

Zhang

Liu

et al. 2020

Front. Pharmacol.

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Background: As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial antitumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored. Methods: We used cell proliferation assay, scratch and transwell experiments, and cell cycle and apoptosis analyses to observe the intervention effect of podophyllotoxin on breast cancer. Furthermore, we analyzed the differences between GSE31448, GSE65194, and GSE45827 in the Gene Expression Omnibus database (GEO) and explored the differential genes using a STRING database. Centiscape2.2, MCODE cluster analysis and KEGG pathway analysis were used to identify the most significant gene differences. Next, we utilized BATMAN-TCM and TCMSP databases for further screening to identify key genes. Finally, quantitative RT-PCR (qRT-PCR) and Western blotting were performed to detect the expression of key targets. Results: Our research confirmed that podophyllotoxin could not only inhibit the migration and invasion of triple-negative breast cancer but also affect the cell cycle and induce apoptosis. In total, 566 differential genes were obtained by using the GEO database. After topological network analysis, cluster analysis, and molecular docking screening, we finally identified PLK1, CCDC20, and CDK1 as key target genes. The results of the qRT-PCR assay showed that the mRNA levels of PLK1, CDC20, and CDK1 decreased, while the expression of upstream P53 increased, after drug induction. The Gene Set Enrichment Analysis (GSEA) and conetwork analysis showed that PLK1 is a more critical regulatory factor. Further Western blotting analysis revealed that there was a negative regulatory relationship between the key gene PLK1 and P53 on the protein level. The results were presented as the mean ± standard deviation of triplicate experiments and P<0.05 was considered to indicate a statistically significant difference. Conclusion: Podophyllotoxin has an intervention effect on the development of triplenegative breast cancer. The expression of PLK1, CDC20, and CDK1 in the cell cycle

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“…Podophyllotoxin isolated from resin of Podophyllum peltatum was found to be too toxic to host so its derivatives were made [103]. Etoposide and teniposide are two semi-synthetic derivatives of epipodophyllotoxin and are used in the treatment of lymphomas, bronchial and testicular cancers [100] [102] [103] [104]. The epipodophyllotoxin binds tubulin, causing DNA strand breaks during the G2 phase of the cell cycle by irreversibly inhibiting DNA topoisomerase II [103].…”

Section: Traditional Medicine and Anti-cancer Propertiesmentioning

confidence: 99%

Naturally Derived Formulations and Prospects towards Cancer

Masarkar¹,

Mukherjee²,

Goel³

et al. 2019

Health

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Traditional Medicine (TM) and their secondary metabolites are being increasingly recognized as useful complementary treatments toward the cancer. A large number of clinical studies have reported and proven concern of cancer patients. Here we have also reported recent studies on the biochemical and cellular mechanisms of Traditional Medicine (TM). Nowadays, Chemotherapy and surgery are standard methods for treatment of cancer, but still it's not been fully successful. Some progress has been made in cancer diagnosis and treatment, but high incidence rate of cancer and low survival rate of patient are still being reported worldwide. Since ancient times, a number of traditional medicines known as Ayurveda, Siddha, Unani, Iranian, Chinese, Korean, acupuncture, Muti, Ifa, and African medicine are widely used for therapeutic purposes and are becoming popular as Traditional Medicine (TM). It has been reported that plants synthesize plethora of "secondary metabolites" or "phytochemicals", proven to possess anti-mutagenic and anti-cancer properties in many research studies. There are many possibilities for further organized research for screening of medicinal plants for their potential and efficacy against chronic diseases such as a cancer and other inflammatory diseases. Therefore, researcher's interest should be in identification and standardization of new anti-cancer drug with low side effects and greater efficacy, that is easily acceptable in medical community and which may overcome the challenges in present and future cancer therapy. This review explores therapeutic value of certain bio-active principals of plant which could serve as potential pharmacologically active drug for treatment of cancer in future.

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Pharmaceutical and pharmacological approaches for bioavailability enhancement of etoposide

Cited by 28 publications

References 48 publications

DNA topoisomerases as molecular targets for anticancer drugs

DNA topoisomerases as molecular targets for anticancer drugs

Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer

Naturally Derived Formulations and Prospects towards Cancer

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