Correction to Apratoxin E, a Cytotoxic Peptolide from a Guamanian Collection of the Marine Cyanobacterium <i>Lyngbya bouillonii</i>

Matthew, Susan; Schupp, Peter J.; Luesch, Hendrik

doi:10.1021/acs.jnatprod.7b00982

Cited by 4 publications

(3 citation statements)

References 1 publication

(1 reference statement)

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“…Apratoxins are potent cytotoxic agents derived from marine cyanobacteria. [16,[32][33][34][35][36] Apratoxin A was the first compound discovered in apratoxin family which possesses broadspectrum differential in vitro activities. [17] Its cytotoxicity is due to potent inhibition of cotranslational translocation [21] at the level of the Sec61 translocon, [22,31] leading to both downregulation of various receptor tyrosine kinases and reduced growth factor secretion.…”

Section: Discussionmentioning

confidence: 99%

Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model

et al. 2018

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Despite the significant progress in the field of cancer therapeutics, the incidence of pancreatic cancer (PC) has continuously increased. One possible mechanism for this increasing burden is impaired drug delivery and drug resistance resulting from a unique tumor microenvironment and genetic mutations. Apratoxins are potent anticancer agents and cotranslational translocation inhibitors with potential therapeutic applications to treat cancers with active secretory pathways. Here, we developed apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent which potently inhibited the growth of both established and patient-derived primary pancreatic cancer cells. We validated its mechanism of action on pancreatic cancer cells by demonstrating the downregulation of multiple receptor tyrosine kinases and inhibition of growth factor and cytokine secretion. Apra S10 also inhibited a number of cytokines secreted by stromal cells, suggesting that Apra S10 not only inhibited pancreatic cancer cell secretion, but also reduced the level of factors secreted by other cell types active within the tumor microenvironment. As Apra S10 tissue distribution indicated its high enrichment in pancreas tissue, an orthotopic pancreatic patient-derived xenograft mouse model that closely mimics the human pancreatic tumor microenvironment was for the first time used in apratoxin studies. Apra S10 showed promising antitumor effect in this pancreatic cancer model and this effect was mediated through anti-proliferation properties.

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Section: Discussionmentioning

confidence: 99%

Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model

et al. 2018

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“…Apratoxins, a class of cyclodepsipeptide isolated from marine cyanobacteria, have been shown to have potent anticancer activity against several cancer cell lines in vitro (3)(4)(5)(6). However, the mode of action for apratoxins is different from current known standard agents (7).…”

Section: Introductionmentioning

confidence: 99%

Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61

Huang

Chen

Jiang

et al. 2016

Molecular Cancer Therapeutics

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Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo. Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A-treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a 3 H-labeled apratoxin A probe and specific Sec 61a/b antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure.

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“…Originally isolated from multiple species of the genus Lyngbya , apratoxins are cyclic depsipeptides composed of peptides and polyketide fragments with known cytotoxic activity [ 21 ]. Several apratoxins have been recognized to date and studied in vivo ( Section 3.1 ) [ 31 , 40 , 41 , 42 ].…”

Section: Depsipeptides With a Recognized Mechanism Of Targeting Cance...mentioning

confidence: 99%

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

2023

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Cancer is currently considered one of the most threatening diseases worldwide. Diet could be one of the factors that can be enhanced to comprehensively address a cancer patient’s condition. Unfortunately, most molecules capable of targeting cancer cells are found in uncommon food sources. Among them, depsipeptides have emerged as one of the most reliable choices for cancer treatment. These cyclic amino acid oligomers, with one or more subunits replaced by a hydroxylated carboxylic acid resulting in one lactone bond in a core ring, have broadly proven their cancer-targeting efficacy, some even reaching clinical trials and being commercialized as “anticancer” drugs. This review aimed to describe these depsipeptides, their reported amino acid sequences, determined structure, and the specific mechanism by which they target tumor cells including apoptosis, oncosis, and elastase inhibition, among others. Furthermore, we have delved into state-of-the-art in vivo and clinical trials, current methods for purification and synthesis, and the recognized disadvantages of these molecules. The information collated in this review can help researchers decide whether these molecules should be incorporated into functional foods in the near future.

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Correction to Apratoxin E, a Cytotoxic Peptolide from a Guamanian Collection of the Marine Cyanobacterium Lyngbya bouillonii

Cited by 4 publications

References 1 publication

Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model

Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model

Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

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