Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins

Sahm, Bianca Del Bianco; Peres, Jade; Rezende‐Teixeira, Paula; Santos, Eduardo Natalino dos; Branco, Paola Cristina; Bauermeister, Anelize; Kimani, Serah; Bisi-Alves, Renata; Bellis, Claire; Mlaza, Mihlali; Jimenez, Paula Christine; Lopes, Norberto P.; Machado-Santelli, Gláucia Maria; Prince, Sharon; Costa-Lotufo, Letı́cia V.

doi:10.3389/fchem.2020.00110

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…Another promising finding was the description of the transcription factor TBX2 modulation by chromomycins (Sahm et al 2020). Using a bioaffinity chromatography technique, it was evidenced that chromomycin A5 (Figure 3) was able to directly bind TBX2.…”

Section: Marine Invertebrates and Microbiotamentioning

confidence: 98%

Bioprospecting macroalgae, marine and terrestrial invertebrates & their associated microbiota

et al. 2022

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The present review aims the discussion of the impact of the bioprospection initiative developed by the projects associated to BIOprospecTA, a subprogram of the program BIOTA, supported by FAPESP. This review brings a summary of the main results produced by the projects investigating natural products (NPs) from non-plants organisms, as examples of the success of this initiative, focusing on the progresses achieved by the projects related to NPs from macroalgae, marine invertebrates, arthropods and associated microorganisms. Macroalgae are one of the most studied groups in Brazil with the isolation of many bioactive compounds including lipids, carotenoids, phycocolloids, lectins, mycosporine-like amino acids and halogenated compounds. Marine invertebrates and associated microorganisms have been more systematically studied in the last thirty years, revealing unique compounds, with potent biological activities. The venoms of Hymenopteran insects were also extensively studied, resulting in the identification of hundreds of peptides, which were used to create a chemical library that contributed for the identification of leader models for the development of antifungal, antiparasitic, and anticancer compounds. The built knowledge of Hymenopteran venoms permitted the development of an equine hyperimmune serum anti honeybee venom. Amongst the microorganisms associated with insects the bioprospecting strategy was to understand the molecular basis of intra- and interspecies interactions (Chemical Ecology), translating this knowledge to possible biotechnological applications. The results discussed here reinforce the importance of BIOprospecTA program on the development of research with highly innovative potential in Brazil.

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Section: Marine Invertebrates and Microbiotamentioning

confidence: 98%

Bioprospecting macroalgae, marine and terrestrial invertebrates & their associated microbiota

et al. 2022

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“…Natural products and compounds derived from natural products account for about 40% of all drugs approved for clinical use, among which ∼70% of anticancer drugs are derived from natural products. ( Butler et al, 2014 ; Newman and Cragg, 2016 ; Bahman et al, 2018 ; Sahm et al, 2020 ). After years of efforts, natural products have also made great progress in anti-cancer, and many natural small molecules have been successfully marketed and become star therapeutic drugs in the corresponding field.…”

Section: Part 3: the Anti-cancer Effect Of Nature Products By Regulat...mentioning

confidence: 99%

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

et al. 2022

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N6-methyladenosine (m6A) RNA methylation is identified as the most common, abundant and reversible RNA epigenetic modification in messenger RNA (mRNA) and non-coding RNA, especially within eukaryotic messenger RNAs (mRNAs), which post-transcriptionally directs many important processes of RNA. It has also been demonstrated that m6A modification plays a pivotal role in the occurrence and development of tumors by regulating RNA splicing, localization, translation, stabilization and decay. Growing number of studies have indicated that natural products have outstanding anti-cancer effects of their unique advantages of high efficiency and minimal side effects. However, at present, there are very few research articles to study and explore the relationship between natural products and m6A RNA modification in tumorigenesis. m6A is dynamically deposited, removed, and recognized by m6A methyltransferases (METTL3/14, METTL16, WTAP, RBM15/15B, VIRMA, CBLL1, and ZC3H13, called as “writers”), demethylases (FTO and ALKBH5, called as “erasers”), and m6A-specific binding proteins (YTHDF1/2/3, YTHDC1/2, IGH2BP1/2/3, hnRNPs, eIF3, and FMR1, called as “readers”), respectively. In this review, we summarize the biological function of m6A modification, the role of m6A and the related signaling pathway in cancer, such as AKT, NF-kB, MAPK, ERK, Wnt/β-catenin, STAT, p53, Notch signaling pathway, and so on. Furthermore, we reviewed the current research on nature products in anti-tumor, and further to get a better understanding of the anti-tumor mechanism, thus provide an implication for nature products with anti-cancer research by regulating m6A modification in the future.

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“…Chromomycins are typically known to bind DNA, causing inhibition of replication and transcription and further induction of programmed cell death. In addition to the DNA-binding properties, CA 5 , through a target-directed approach, was shown to bind the transcription factor TBX2, which impacts the cytotoxic activity of this compound [78]. The TBX2 transcription factor is overexpressed in several types of cancer and contributes to increased cell proliferation and bypass of senescence and, therefore, has been considered a potential target for new anticancer therapies (▶ Fig.…”

Section: Cnidariansmentioning

confidence: 99%

Anticancer Potential of Compounds from the Brazilian Blue Amazon

et al. 2020

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Abstract“Blue Amazon” is used to designate the Brazilian Economic Exclusive Zone, which covers an area comparable in size to that of its green counterpart. Indeed, Brazil flaunts a coastline spanning 8000 km through tropical and temperate regions and hosting part of the organisms accredited for the countryʼs megadiversity status. Still, biodiversity may be expressed at different scales of organization; besides species inventory, genetic characteristics of living beings and metabolic expression of their genes meet some of these other layers. These metabolites produced by terrestrial creatures traditionally and lately added to by those from marine organisms are recognized for their pharmaceutical value, since over 50% of small molecule-based medicines are related to natural products. Nonetheless, Brazil gives a modest contribution to the field of pharmacology and even less when considering marine pharmacology, which still lacks comprehensive in-depth assessments toward the bioactivity of marine compounds so far. Therefore, this review examined the last 40 years of Brazilian natural products research, focusing on molecules that evidenced anticancer potential–which represents ~ 15% of marine natural products isolated from Brazilian species. This review discusses the most promising compounds isolated from sponges, cnidarians, ascidians, and microbes in terms of their molecular targets and mechanisms of action. Wrapping up, the review delivers an outlook on the challenges that stand against developing groundbreaking natural products research in Brazil and on a means of surpassing these matters.

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Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins

Cited by 10 publications

References 36 publications

Bioprospecting macroalgae, marine and terrestrial invertebrates & their associated microbiota

Bioprospecting macroalgae, marine and terrestrial invertebrates & their associated microbiota

The Role of m6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

Anticancer Potential of Compounds from the Brazilian Blue Amazon

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