Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Kai-Yao

doi:10.2174/1568026615666150414120547

Cited by 58 publications

(49 citation statements)

References 114 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several findings in the tissue-specific distributions of the tested fluorescent compounds predict that they may possess potential side-effects. For example, vinblastine, an alkaloid from Vinca rosea , has been used as a classical chemotherapeutic drug for its inhibition of tubulin polymerization into microtubules in highly proliferating cells ( Karnofsky, 1964 ; Zhou and Rahmani, 1992 ; Lee et al, 2015 ). Here, we observed that vinblastine accumulated significantly in zebrafish otolith, a biomineralized structure critical for hearing and balance in teleosts, predicting possible damage to the auditory senses ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Screening in larval zebrafish reveals tissue-specific distributions of fifteen fluorescent compounds

Yao

Sun

Fei

et al. 2017

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds.

show abstract

Section: Resultsmentioning

confidence: 99%

Screening in larval zebrafish reveals tissue-specific distributions of fifteen fluorescent compounds

Yao

Sun

Fei

et al. 2017

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Catharanthus alkaloids are among the most widely used chemotherapy reagents for various tumour therapies; however, they exhibit side effects. To reduce their toxicity and enhance the therapeutic efficiency of these compounds, liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations were used [ 23 ]. Catharanthus alkaloids are used in chemotherapy to treat breast cancer, ovarian cancer, non-small cell lung cancer, and soft tissue sarcoma (orphan).…”

Section: The Catharanthus Alkaloidsmentioning

confidence: 99%

Anticancer Activity of Natural Compounds from Plant and Marine Environment

Lichota

Gwoździński

2018

IJMS

335

198

View full text Add to dashboard Cite

This paper describes the substances of plant and marine origin that have anticancer properties. The chemical structure of the molecules of these substances, their properties, mechanisms of action, their structure–activity relationships, along with their anticancer properties and their potential as chemotherapeutic drugs are discussed in this paper. This paper presents natural substances from plants, animals, and their aquatic environments. These substances include the vinca alkaloids, mistletoe plant extracts, podophyllotoxin derivatives, taxanes, camptothecin, combretastatin, and others including geniposide, colchicine, artesunate, homoharringtonine, salvicine, ellipticine, roscovitine, maytanasin, tapsigargin, and bruceantin. Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from the marine plants and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates (e.g., sponges, tunicates, and soft corals) as well as certain other substances that have been tested on cells and experimental animals and used in human chemotherapy.

show abstract

“…Vinca alkaloids, including vinblastine, vincristine, vinflunine, vinorelbine and vindesine, are tubulin-binding agents that have been widely used as antitumor therapy in the treatment of breast cancer, osteosarcoma and acute lymphocytic leukemia, either as a single agent or in combination with other drugs 7 - 9 . They have been considered cell cycle-specific cytotoxic drugs that bind to the vinblastine-binding site on tubulin, prevent microtubule polymerization, cause metaphase arrest and inhibit mitosis in cancer cells, leading to cell death 10 , 11 . Vinca alkaloids also exert potent antiangiogenic effects by inhibiting endothelial cell motility 12 , suppressing Rac1 and Cdc42 activity 13 , down-regulating vascular endothelial growth factor receptor-2 expression 14 or disturbing EB1 localization 15 .…”

Section: Introductionmentioning

confidence: 99%

Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization

et al. 2018

View full text Add to dashboard Cite

Vinca alkaloids, the well-known tubulin-binding agents, are widely used for the clinical treatment of malignant tumors. However, little attention has been paid to their vascular disrupting effects, and the underlying mechanisms remain largely unknown. This study aims to investigate the vascular disrupting effect and the underlying mechanisms of vinca alkaloids.Methods: The capillary disruption assay and aortic ring assay were performed to evaluate the in vitro vascular disrupting effect of desacetylvinblastine monohydrazide (DAVLBH), a derivate of vinblastine, and the in vivo vascular disrupting effect was assessed on HepG2 xenograft model using magnetic resonance imaging, hematoxylin and eosin staining and immunohistochemistry. Tubulin polymerization, endothelial cell monolayer permeability, western blotting and immunofluorescence assays were performed to explore the underlying mechanisms of DAVLBH-mediated tumor vascular disruption.Results: DAVLBH has potent vascular disrupting activity both in vitro and in vivo. DAVLBH disrupts tumor vessels in a different manner than classical tubulin-targeting VDAs; it inhibits microtubule polymerization, promotes the internalization of vascular endothelial cadherin (VE-cadherin) and inhibits the recycling of internalized VE-cadherin to the cell membrane, thus increasing endothelial cell permeability and ultimately resulting in vascular disruption. DAVLBH-mediated promotion of VE-cadherin internalization and inhibition of internalized VE-cadherin recycling back to the cell membrane are partly dependent on inhibition of microtubule polymerization, and Src activation is involved in DAVLBH-induced VE-cadherin internalization.Conclusions: This study sheds light on the tumor vascular disrupting effect and underlying mechanisms of vinca alkaloids and provides new insight into the molecular mechanism of tubulin-targeting VDAs.

show abstract

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

Cited by 58 publications

References 114 publications

Screening in larval zebrafish reveals tissue-specific distributions of fifteen fluorescent compounds

Screening in larval zebrafish reveals tissue-specific distributions of fifteen fluorescent compounds

Anticancer Activity of Natural Compounds from Plant and Marine Environment

Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization

Contact Info

Product

Resources

About