Synergistic effect of a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, and paclitaxel on human multidrug resistance cancer cell lines

Xia

2021

IJMS

Cyclopeptides or cyclic peptides are polypeptides formed by ring closing of terminal amino acids. A large number of natural cyclopeptides have been reported to be highly effective against different cancer cells, some of which are renowned for their clinical uses. Compared to linear peptides, cyclopeptides have absolute advantages of structural rigidity, biochemical stability, binding affinity as well as membrane permeability, which contribute greatly to their anticancer potency. Therefore, the discovery and development of natural cyclopeptides as anticancer agents remains attractive to academic researchers and pharmaceutical companies. Herein, we provide an overview of anticancer cyclopeptides that were discovered in the past 20 years. The present review mainly focuses on the anticancer efficacies, mechanisms of action and chemical structures of cyclopeptides with natural origins. Additionally, studies of the structure–activity relationship, total synthetic strategies as well as bioactivities of natural cyclopeptides are also included in this article. In conclusion, due to their characteristic structural features, natural cyclopeptides have great potential to be developed as anticancer agents. Indeed, they can also serve as excellent scaffolds for the synthesis of novel derivatives for combating cancerous pathologies.

Section: Anticancer Cyclopeptides Derived From Non-marine Fungimentioning

confidence: 99%

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

Xia

2021

IJMS

“…In general, these depsipeptides potently activate caspase-3, Fas/FasL, p21, and p27, and inhibit histone deacetylases, all of which result in pro-apoptotic signaling [ 27 , 28 , 29 , 30 ] Here, we present the state-of-the-art on depsipeptides that induce apoptosis in tumor cells ( Table 1 and Figure 2 ).…”

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

confidence: 99%

“…In vitro, it inhibited the growth of human lung cancer cells (A549), ovarian cancer cells (SK-OV-3), melanoma (SK-MEL-2), and uterine sarcoma (MES-SA) cells with IC 50 values ranging from 10 to 14.74 μM [ 13 ]. Specifically, this novel depsipeptide inhibited topoisomerase I and inhibited the growth of colorectal carcinoma (HCT-15) cells [ 28 ].…”

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

confidence: 99%

See 1 more Smart Citation

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

2023

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.

Bioscience, Biotechnology, and Biochemistry

“…20) Interestingly, one isolate (Fusarium solani KCCM90040) produced a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, which exhibited in vitro cytotoxic effects on human cancer cell lines. 21) In general, efficiency of secondary metabolite production from fungus is influenced by multiple parameters such as temperature, growth time, nutrition; their effects may be either independent or interactive. 22) Therefore, the production of neoN-methylsansalvamide can be effected by environmental conditions.…”

Section: )mentioning

confidence: 99%

Optimization of culture conditions of Fusarium solani for the production of neoN-methylsansalvamide

Lee

Phat

Nam

et al. 2014

Self Cite

The aim of this study was to optimize the culture conditions of Fusarium solani KCCM90040 on cereal grain for the production of neoN-methylsansalvamide, a novel low-molecular-weight cyclic pentadepsipeptide exhibiting cytotoxic and multidrug resistance reversal effects. From the analysis of variance results using response surface methodology, temperature, initial moisture content, and growth time were shown to be important parameters for the production of neoN-methylsansalvamide on cereal grain. A model was established in the present study to describe the relationship between environmental conditions and the production of neoN-methylsansalvamide on rice, the selected cereal grain. The optimal culture conditions were determined at 25.79°C with the initial moisture content of 40.79%, and 16.19 days of growth time. This report will give important information concerning the optimization of environmental conditions using statistic methodology for the production of a new cyclic pentadepsipeptide from fungi.Key words: cyclic pentadepsipeptides; Fusarium solani; environmental conditions; response surface methodology Various reviews of peptides from fungi have revealed that Fusarium strains found in fungi-infected plants produce several cyclic depsipeptides such as beauvericin, 1) enniatins, 2,3) zygosporamide, 4) and neosansalvamide analogs 5,6) via the non-ribosomal peptide synthesis system. 7,8) These cyclic depsipetides exhibit numerous pharmaceutical benefits such as cytotoxic, 9,10) antifungal, 11) and antibiotic 1) effects as well as calcium channel antagonism.12) Another cytotoxic cyclic pentadepsipeptides, sansalvamide analogs, were produced by Fusarium strains. 13,14) Sansalvamide A was first reported from the marine micro-organism Halodule wrightii, 14)This N-methylated sansalvamide exhibited in vitro cytotoxicity in a National Cancer Institute human tumor cell line screen (EC 50 = 8.3 μmol).14) Sansalvamide showed cytototoxic potency against HCT116 (colon carcinoma), COLO205 (colon), and SK-MEL-2 (melanoma) cancer cell lines with EC 50 values of 9.8, 3.5, and 5.9 μg/mL, respectively. 13) Sansalvamide and its analogs, which were produced by organic synthesis, caused marked time-and concentration-dependent inhibition of DNA synthesis and cell proliferation of human pancreatic cancer cell lines. [15][16][17] Furthermore, sansalvamide and its analogs showed a strong cytotoxic effect against multidrug resistance (MDR) human colon cancer cell lines.18) These anticancer effects of sansalvamide analogs can be attributed to their inhibition of topoisomerase I, and their cytotoxicity may be mediated by this mechanism.17,19) Sansalvamide analogs exhibited cytotoxic activity against human cancer cell lines, suggesting that they could be valuable therapeutic agents. 17,18) Our research group isolated several Fusarium strains producing different cyclic depsipeptides including enniatins H, I, and MK1688 with beauvericin. 20) Interestingly, one isolate (Fusarium solani KCCM90040) produced a novel cyclic pentadepsipeptide, n...