Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

Natsume, Tsugitaka; Watanabe, Junichi; Ogawa, Kenji; Yasumura, Kazuhiko; Kobayashi, Motohiro

doi:10.1111/j.1349-7006.2007.00418.x

Cited by 18 publications

(15 citation statements)

References 23 publications

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“…Compounds that inhibit the abnormal growth of cancer cells by blocking the DNA repair process or functioning as antimicrotubule agents are useful cancer treatments [117,118]. Many compounds isolated from marine sponges, including soblidotin and spongistatins, exhibit potent cytotoxic activities toward several cancer cell lines; these activities are associated with the abilities of these compounds to disturb microtubule homeostasis and to evade the DNA repair system [119][120][121].…”

Section: Discussionmentioning

confidence: 99%

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

et al. 2019

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Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative effects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative effects and induced cell cycle arrest at the G2/M transition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis.

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Section: Discussionmentioning

confidence: 99%

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

et al. 2019

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“…Soblidotin (TZT-1027) ( Figure 2 ), which is in phase II trials, is an microtubule active drug derived from the antimitotic dolastatin-10, which was isolated from the sea hare Dolabella auricularia , that specifically damages tumor vasculatures by exerting a considerable antivascular effect along with an excellent cytotoxic effect [ 106 ]. Tasidotin ( Table 2 and Figure 2 ), or synthadotin (ILX-651), is a water-soluble dolastatin pentapeptide derivate [ 107 ] with microtubule targeting activity in advanced solid tumors [ 107 ] and is also in phase II trials.…”

Section: Mnp-based Drugs That Are Approved or In Ongoing Clinical mentioning

confidence: 99%

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs

et al. 2017

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Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes.

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“…To address these questions, we have used the only soluble αβ‐tubulin complex shown so far to yield crystals that diffract to a sufficient resolution to identify bound ligands, namely a complex with the RB3 stathmin‐like domain (RB3‐SLD). We report the 4.1Å and 3.8 Å resolution X‐ray structures of tubulin–colchicine‐RB3‐SLD [(Tc) 2 R] (Ravelli et al , 2004) in complex with two vinca domain antimitotic peptides, phomopsin A (Tonsing et al , 1984) and soblidotin (Natsume et al , 2007; a dolastatin 10 analogue also named TZT‐1027 or auristatin PE; Fig 1A; supplementary Table 1 online). In addition to clarifying the relationship of the vinca domain ligand‐binding sites and their mechanisms of microtubule inhibition, the structures elucidate the structural mechanism for GTP exchange on tubulin.…”

Section: Introductionmentioning

confidence: 99%

Structural insight into the inhibition of tubulin by vinca domain peptide ligands

et al. 2008

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The tubulin vinca domain is the target of widely different microtubule inhibitors that interfere with the binding of vinblastine. Although all these ligands inhibit the hydrolysis of GTP, they affect nucleotide exchange to variable extents. The structures of two vinca domain antimitotic peptides-phomopsin A and soblidotin (a dolastatin 10 analogue)-bound to tubulin in a complex with a stathmin-like domain show that their sites partly overlap with that of vinblastine and extend the definition of the vinca domain. The structural data, together with the biochemical results from the ligands we studied, highlight two main contributors in nucleotide exchange: the flexibility of the tubulin subunits' arrangement at their interfaces and the residues in the carboxy-terminal part of the b-tubulin H6-H7 loop. The structures also highlight common features of the mechanisms by which vinca domain ligands favour curved tubulin assemblies and destabilize microtubules.

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Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

Cited by 18 publications

References 23 publications

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs

Structural insight into the inhibition of tubulin by vinca domain peptide ligands

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