Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic <i>nu</i>/<i>nu</i> Mouse Model

Meyer, Colin; Krauth, Melissa; Wick, Michael J.; Shay, Jerry W.; Gellert, Ginelle C.; Brabander, Jef K. De; Northcote, Peter T.; Miller, John H.

doi:10.1158/1535-7163.mct-15-0167

Cited by 29 publications

(28 citation statements)

References 34 publications

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“…However, the combination therapy of peloruside A plus docetaxel or paclitaxel resulted in high toxicity and mortality [ 146 ]. In a further study performed on Pgp–overexpressing ovarian xenografted-bearing mice, peloruside A was less effective in tumor growth inhibition than doxorubicin and paclitaxel; it was, however, better tolerated, with 14% of animal death against 43% recorded for the reference drugs [ 146 ]. Currently, clinical studies are on standby due to the limited quantities of peluroside A obtained from natural matrix.…”

Section: Antiproliferative Effectsmentioning

confidence: 99%

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

et al. 2017

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Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy.

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Section: Antiproliferative Effectsmentioning

confidence: 99%

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

et al. 2017

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“…The V7 and V8 peptides are only parts of the VEGI174 protein, and their spatial structures and biological functions are different; therefore, these features require more intensive study. Any drug resulting in a TGI of ≥58% (the National Cancer Institute standard criterion for antitumour activity) is considered a valid anticancer agent (37). VEGI174, V7 and V8 have exerted potential antitumour effects in vivo.…”

Section: Discussionmentioning

confidence: 99%

VEGI174 protein and its functional domain peptides exert antitumour effects on renal cell carcinoma

et al. 2018

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Vascular endothelial growth inhibitor (VEGI) has been identified as an anti-angiogenic cytokine. However, the effects of VEGI174 protein, and its functional domain peptides V7 and V8, on renal cell carcinoma (RCC) remain unknown. In the present study, the protein and peptides were biosynthesised as experimental agents. The A498 and 786-O RCC cell lines, and an established mouse xenograft model, were separately treated with VEGI174, V7 or V8. Cellular functions, including proliferation, migration and invasion, were subsequently detected. Cell migration and invasion were monitored using the xCELLigence system. Furthermore, tumour growth and mouse behaviours, including mobility, appetite and body weight, were assessed. The results demonstrated that VEGI174, V7 and V8 inhibited the proliferation, migration and invasion of A498 and 786-O cell lines when administered at concentrations of 1 and 100 pM, 10 nM and 1 µM. The inhibitory effects exhibited dose-and time-dependent antitumour activity. Furthermore, VEGI174, V7 and V8 inhibited tumour growth in A498 and 786-O xenograft mice. In the A498 xenografts, the tumour growth inhibition (TGI) rates in the VEGI174-, V7-and V8-treated groups were 71, 20 and 31%, respectively. In the 786-O xenografts, the TGI rates in the VEGI174-, V7-and V8-treated groups were 34, 26 and 31%, respectively. There was no significant loss in body weight and no cases of mortality were observed for all treated mice. In conclusion, VEGI174, V7 and V8 exhibited potential antitumour effects and were well tolerated in vivo. V7 and V8, as functional domain peptides of the VEGI174 protein, may be studied for the future treatment of RCC.

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“…At a dose of 5 mg·kg −1 , 84% inhibition of tumor growth was achieved, whereas compound 9 (8 mg·kg −1 ) inhibited tumor growth only down to 50%. In addition, for A549 cell xenografts, compound 12a displayed better results than compound 9 (44% inhibition at the dose of 16 mg·kg −1 ); the tumor growth inhibition ranged between 51% and 74% depending on the type of dosing (5–15 mg·kg −1 ) [ 105 ].…”

Section: Microtubule Inhibitorsmentioning

confidence: 99%

Mitotic Poisons in Research and Medicine

et al. 2020

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Cancer is one of the greatest challenges of the modern medicine. Although much effort has been made in the development of novel cancer therapeutics, it still remains one of the most common causes of human death in the world, mainly in low and middle-income countries. According to the World Health Organization (WHO), cancer treatment services are not available in more then 70% of low-income countries (90% of high-income countries have them available), and also approximately 70% of cancer deaths are reported in low-income countries. Various approaches on how to combat cancer diseases have since been described, targeting cell division being among them. The so-called mitotic poisons are one of the cornerstones in cancer therapies. The idea that cancer cells usually divide almost uncontrolled and far more rapidly than normal cells have led us to think about such compounds that would take advantage of this difference and target the division of such cells. Many groups of such compounds with different modes of action have been reported so far. In this review article, the main approaches on how to target cancer cell mitosis are described, involving microtubule inhibition, targeting aurora and polo-like kinases and kinesins inhibition. The main representatives of all groups of compounds are discussed and attention has also been paid to the presence and future of the clinical use of these compounds as well as their novel derivatives, reviewing the finished and ongoing clinical trials.

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Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model

Cited by 29 publications

References 34 publications

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

VEGI174 protein and its functional domain peptides exert antitumour effects on renal cell carcinoma

Mitotic Poisons in Research and Medicine

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