Topoisomerase inhibitors as anti-arthritic agents

Jackson, John K.; Higo, Tobi; Hunter, William L.; Burt, Helen M.

doi:10.1007/s00011-007-7163-6

Cited by 43 publications

(40 citation statements)

References 37 publications

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“…The present study focused on β-lap, a natural quinone derived from the bark of the Lapacho tree (12,13). Previous studies have revealed that β-lap acts as a potent anti-proliferative agent, inhibiting topoisomerase I/II (26,32,33), specificity protein 1 (26) and the cell cycle (34). It has also been shown that repetitive oxidation-reduction of β-lap by NQO1 generates ROS in tumor cells (14), thus contributing to cytotoxicity in malignancies, including pancreatic cancer (35,36).…”

Section: Discussionmentioning

confidence: 99%

Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines

et al. 2017

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Abstract. NAD(P)H quinone oxidoreductase 1 (NQO1)-dependent antitumor drugs such as β-lapachone (β-lap) are attractive candidates for cancer chemotherapy because several tumors exhibit higher expression of NQO1 than adjacent tissues. Although the association between NQO1 and β-lap has been elucidated, the effects of a NQO1-inducer and β-lap used in combination remain to be clarified. It has previously been reported that melanoma cell lines have detectable levels of NQO1 expression and are sensitive to NQO1-dependent drugs such as 17-allylamino-17-demethoxygeldanamycin. The present study was conducted to investigate the involvement of NQO1 in β-lap-mediated toxicity and the utility of combination treatment with a NQO1-inducer and β-lap in malignant melanoma cell lines. Decreased expression or inhibition of NQO1 caused these cell lines to become less sensitive to β-lap, indicating a requirement of NQO1 activity for β-lap-mediated toxicity. Of note was that carnosic acid (CA), a compound extracted from rosemary, was able to induce further expression of NQO1 through NF-E2 related factor 2 (NRF2) stabilization, thus significantly enhancing the cytotoxicity of β-lap in all of the melanoma cell lines tested. Taken together, the data presented in the current study indicated that the NRF2-NQO1 axis may have potential value as a therapeutic target in malignant melanoma to improve the rate of clinical response to NQO1-dependent antitumor drugs. IntroductionMalignant melanoma is one of the most aggressive forms of cancer, exhibiting resistance to various forms of chemotherapy.The global incidence and mortality rates of malignant melanoma are increasing (1-3). Novel targeted therapies designed to kill melanoma cells harboring mutations in B-Raf proto-oncogene, serine/threonine kinase (BRAF) have been developed using vemurafenib, which is a specific BRAF inhibitor (4,5). Missense mutations to the BRAF gene, most commonly a valine-to-glutamic acid substitution at codon 600, has been observed in ~80% of melanocytic nevi and ~50% of melanomas (6-9). In addition to this BRAF mutation, another therapeutic target has been investigated, as melanomas, including acral lentiginous melanoma, the most common type in ethnicities that produce high levels of melanin, have a low frequency of BRAF gene mutation (10,11). However, details of the mechanism responsible for the drug insensitivity of melanomas lacking BRAF mutations have been largely unclear. On the basis of the aforementioned background, a search for novel therapeutic strategies is justified.β-lapachone (β-lap), a lipophilic cytotoxic o-naphtoquinone derived from the bark of the South American Lapacho tree (Tabebuia avellanedae), has recently attracted attention as an antitumor drug (12,13). The mechanism of its antitumor effect is considered to involve the formation of reactive oxygen species (ROS) (13-15). ROS and other types of radicals are involved in a variety of biological phenomena, including tumorigenesis, degenerative disease and aging (16,17), and are also important medi...

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Section: Discussionmentioning

confidence: 99%

Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines

et al. 2017

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“…4B). A predicted connection to rheumatoid arthritis confirms the drug's newly proposed role as an antiarthritic agent (22); a connection to skin disorder reflects its known side effect of skin erupts (23). Most notably, the connection to cardiovascular diseases points to doxorubicin's potentially fatal toxicity to the heart muscles, which is cumulative over the patient's lifetime (24).…”

Section: Resultsmentioning

confidence: 73%

Bayesian approach to transforming public gene expression repositories into disease diagnosis databases

Huang

Liu

Zhou

2010

Proc. Natl. Acad. Sci. U.S.A.

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The rapid accumulation of gene expression data has offered unprecedented opportunities to study human diseases. The National Center for Biotechnology Information Gene Expression Omnibus is currently the largest database that systematically documents the genome-wide molecular basis of diseases. However, thus far, this resource has been far from fully utilized. This paper describes the first study to transform public gene expression repositories into an automated disease diagnosis database. Particularly, we have developed a systematic framework, including a two-stage Bayesian learning approach, to achieve the diagnosis of one or multiple diseases for a query expression profile along a hierarchical disease taxonomy. Our approach, including standardizing cross-platform gene expression data and heterogeneous disease annotations, allows analyzing both sources of information in a unified probabilistic system. A high level of overall diagnostic accuracy was shown by cross validation. It was also demonstrated that the power of our method can increase significantly with the continued growth of public gene expression repositories. Finally, we showed how our disease diagnosis system can be used to characterize complex phenotypes and to construct a disease-drug connectivity map.

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“…Plumbagin has been reported to be a topoisomerase-II inhibitor by displaying inhibitory activities of corresponding enzymes involved in rheumatoid arthritis (RA) (Jackson et al, 2008). Checker et al (2009) reported that plumbagin suppresses NF-kB (ubiquitous transcription factor) activation in tumor cells, and hence might have an effect on biological functions of leukocytes actively participating in various immune responses.…”

Section: Anti-inflammatorymentioning

confidence: 99%

A Comprehensive Review on the Genus Plumbago With Focus on Plumbago Auriculata (Plumbaginaceae)

Singh¹,

Naidoo²,

Baijnath³

2017

Afr J Tradit Complement Altern Med

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Background: The genus Plumbago distributed in warm tropical regions throughout the world is the largest genus in Plumbaginaceae. Medicinal plants are characteristic to the genus Plumbago and are cultivated and utilized worldwide. Plumbago auriculata Lam. is common in South Africa and is often cultivated for its ornamental and medicinal uses throughout the world. Materials and Methods: A comprehensive review of the genus Plumbago with focus on Plumbago auriculata was carried out and information was gathered using scientific publications, conference proceedings, the internet and books. Articles based on the morphology, pharmacological and medicinal uses of Plumbago auriculata was analysed thoroughly. Results: Plumbago auriculata plant parts posses a wide range of phytochemicals with plumbagin being the marker compound showing various pharmacological activities. Different plant parts are claimed to be used for the treatment of human and animal ailments, however they do exhibit toxic properties and need to be administered with caution. Salt secreting glands and trichomes are characteristic of Plumbaginaceae. Conclusion: This study reveals new insights on the genus Plumbago and the potential use of species in the genus as medicinal plants. Plumbago auriculata possess the bioactive compound plumbagin and secondary metabolites, thus, it is of high medicinal importance. P. auriculata is a poorly nor favourite studied species in the genus Plumbago and further research needs to be carried out to explore specific details of the species.

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Topoisomerase inhibitors as anti-arthritic agents

Abstract: These studies support the explorative use of topoisomerase I (particularly camptothecin) and II inhibitors as potential agents for use against RA.

Cited by 43 publications

References 37 publications

Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines

Carnosic acid, an inducer of NAD(P)H quinone oxidoreductase 1, enhances the cytotoxicity of β‑lapachone in melanoma cell lines

Bayesian approach to transforming public gene expression repositories into disease diagnosis databases

A Comprehensive Review on the Genus Plumbago With Focus on Plumbago Auriculata (Plumbaginaceae)

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