A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway

Liu, Shuangwei; Gao, Xian; Zhang, Lisong; Qin, Shuanglin; Wei, Mingming; Liu, Ning; Zhao, Rui; Li, Benlong; Meng, Yijun; Lin, Gang; Cheng, Lü; Liu, Xinhua; Xie, Maodun; Liu, Tongtong; Zhou, Honggang; Qi, Min; Yang, Guang; Yang, Cheng

doi:10.1016/j.ejmech.2018.06.046

Cited by 16 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a consequence, a combination therapy using ALDH inhibitor and chemotherapy is increasing CSCs response [ 218 , 221 ]. Furthermore, ALDH may be used as a marker of therapy efficiency or may be selectively targeted in therapy [ 222 , 223 , 224 , 225 , 226 ].…”

Section: Melanoma Cscs—the Origin Of Heterogeneity Plasticity Aggress...mentioning

confidence: 99%

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

et al. 2022

View full text Add to dashboard Cite

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma’s clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or “inflammasome”, its association with adipose tissue products, including the release of “extracellular vesicles”, and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma’s particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

show abstract

Section: Melanoma Cscs—the Origin Of Heterogeneity Plasticity Aggress...mentioning

confidence: 99%

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A number of anticancer stem cell compounds have been discovered and developed. − As revealed in previous reports, as well as our experiences, the structures with a Michael receptor moiety of optimized natural skeletons may deliver useful compounds that exhibit promising anticancer and anticancer stem cell activities (Figure ). − Notably, novel anti-CSC compounds were achieved by chemical introduction of an enone moiety at the appropriate position of natural triterpenoic acids, which do not possess the structure of Michael receptor originally . Following the previous success, in this study, we identified a novel anticancer stem cell compound 38 from a small compound library that was derived from a natural product Pleuromutilin by the same medicinal chemical modification strategy, which was originally known as a broad-spectrum antibiotic that inhibits the 50S ribosome of bacteria. , Compound 38 could ablate cancer stem cells and unexpectedly induce cancer cell death via necroptosis.…”

Section: Introductionmentioning

confidence: 91%

“…The title compound 20 was obtained following the procedure described for 6 using 3phenoxybenzoic acid (257 mg, 1.20 mmol). Flash column chromatography ( (3aR,4R,5R,7S,8S,9R,9aS,12R)-5-Hydroxy-4,7,9,12-tetramethyl-2methylene-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta [8]annulen-8-yl 4-Bromo-2-methylbenzoate (22). The title compound 22 was obtained following the procedure described for 6 using 4bromobenzoic acid (241 mg, 1.20 mmol).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Malignant melanoma cell line B16F10 was reported as the cell line most sensitive to these synthetic compounds. Compounds 15,17,22, and 38 were selected for a subsequent study with potent anticancer activity. Notably, this indicated that α,β-unsaturated enone moieties were the critical pharmacophore for anticancer activity, because reductive analogue 49 of compound 38 was inactive.…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

Necroptosis has been recently confirmed as a nonapoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing necroptosis of cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound 38) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma cancer cell death via necroptosis. Furthermore, compound 38 noticeably ablated various cancer stem cells and inhibited the growth of melanoma cancer cells both in vitro and in vivo. Moreover, 38 exhibited low toxicity in animal models and excellent PK properties, which is currently being verified as a potential anticancer drug candidate.

show abstract

“…In a study by Liu et al, an anti-cancer stem cells lead molecule, 38, was found to significantly suppress tumor growth both in vitro and in vivo. Moreover, 38 was able to significantly reduce the number of melanoma tumor spheres and decrease the percentage of ALDH+ melanoma cells by blocking the Wnt/β-catenin signaling pathway [97].…”

Section: Falcipain Inhibitorsmentioning

confidence: 99%

Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets

Tan

Phyo

2020

Molecules

View full text Add to dashboard Cite

The prokaryotic filamentous marine cyanobacteria are photosynthetic microbes that are found in diverse marine habitats, ranging from epiphytic to endolithic communities. Their successful colonization in nature is largely attributed to genetic diversity as well as the production of ecologically important natural products. These cyanobacterial natural products are also a source of potential drug leads for the development of therapeutic agents used in the treatment of diseases, such as cancer, parasitic infections and inflammation. Major sources of these biomedically important natural compounds are found predominately from marine cyanobacterial orders Oscillatoriales, Nostocales, Chroococcales and Synechococcales. Moreover, technological advances in genomic and metabolomics approaches, such as mass spectrometry and NMR spectroscopy, revealed that marine cyanobacteria are a treasure trove of structurally unique natural products. The high potency of a number of natural products are due to their specific interference with validated drug targets, such as proteasomes, proteases, histone deacetylases, microtubules, actin filaments and membrane receptors/channels. In this review, the chemistry and biology of selected potent cyanobacterial compounds as well as their synthetic analogues are presented based on their molecular targets. These molecules are discussed to reflect current research trends in drug discovery from marine cyanobacterial natural products.

show abstract

A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway

Cited by 16 publications

References 17 publications

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells

Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets

Contact Info

Product

Resources

About