<i>In Vitro</i>Growth Inhibitory Effects of Cytochalasins and Derivatives in Cancer Cells

Goietsenoven, Gwendoline Van; Mathieu, Véronique; Andolfi, Anna; Cimmino, Alessio; Lefranc, Florence; Kiss, Róbert; Evidente, Antonio

doi:10.1055/s-0030-1250523

Cited by 47 publications

(50 citation statements)

References 33 publications

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“…More than 60 different cytochalasins from several species of fungi have been classified into various subgroups based on the size of the macrocyclic ring and the substituent of the perhydroisoindolyl-1-one residue at the C-3 position [40]. Despite this diversity, only cytochalasins B and D have been extensively studied for their chemotherapeutic potential.…”

Section: Candidate Migrastatic Drugsmentioning

confidence: 99%

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

et al. 2017

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In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.

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Section: Candidate Migrastatic Drugsmentioning

confidence: 99%

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

et al. 2017

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“…These congeners are characterized by a highly substituted perhydro-isoindolone structure that is typically attached to a macrocyclic ring [ 1 ]. More than 60 different cytochalasins from several species of fungi have been classified into various subgroups based on the size of the macrocyclic ring and the substituent of the perhydroisoindolyl-1-one residue at the C-3 position [ 2 ]. However, the most studied congener in regards to antineoplastic activity has been cytochalasin B.…”

Section: Introductionmentioning

confidence: 99%

“…However, the most studied congener in regards to antineoplastic activity has been cytochalasin B. As a microfilament-disrupting agent, cytochalasin B alters cell motility, adherence, secretion, drug efflux, deformability, morphology, and size, among many other effects [ 1 , 2 ]. The effects of cytochalasin B on cell adherence include alteration of cell junctions, leading to changes in tissue physiology and transport.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

et al. 2015

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Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or i.v. to determine whether it could affect the long-term development of an established i.d. tumor. Cytochalasin B was then liposome encapsulated to determine whether the maximum tolerated dose (MTD) of the compound could be increased, while reducing immunosuppression that we have previously characterized. Liposomal cytochalasin B was also administered to mice challenged i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The results can be summarized as follows: 1) cytochalasin B substantially delayed the growth of i.d. M109 tumor nodules, inhibited metastatic progression in surrounding tissues, and produced long-term cures in treated mice; 2) liposomal cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different distribution in tissue concentrations, and displayed antitumor effects against M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show that cytochalasin B exploits unique chemotherapeutic mechanisms and is an effective antineoplastic agent in vivo in pre-clinical models, either in bolus form or after liposome encapsulation.

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“…However, computer-assisted phase-contrast microscopy performed by Van Goietsenoven et al revealed that cytochalasins can be grouped into two categories, i.e., cytotoxic versus cytostatic, indicating that it may be possible to develop novel, non-toxic cytostatic anticancer agents by tuning cytochalasin targets. 27) Our results showed that cytochalasin H isolated from G. sinensis thorns can successfully inhibit the angiogenic properties, such as cell growth, mobility, and 3 dimensional-tube formation (≥125 nmol/L), of HUVEC in vitro, and blood vessel formation by mouse endothelial cells in vivo (≥250 nmol/L) without seriously altering cell viability. The effective doses in our study are relatively low doses when compared with the LD 50 of 12.5 mg/kg that was observed in day-old cockerels.…”

Section: Discussionmentioning

confidence: 66%

Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of <i>Gleditsia sinensis</i> Thorns

Lee

Kim

et al. 2014

Biological & Pharmaceutical Bulletin

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Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.

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In VitroGrowth Inhibitory Effects of Cytochalasins and Derivatives in Cancer Cells

Cited by 47 publications

References 33 publications

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of <i>Gleditsia sinensis</i> Thorns

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