Application of the metabolomics approach to the discovery of active compounds from Brazilian trees against resistant human melanoma cells

Kato, Natália Naomi; Stavis, Vanessa Katherinne; Boaretto, Amanda Galdi; Castro, David; Alves, Flávio Macêdo; Souza, Kely de Picoli; Santos, Edson Lucas dos; Silva, Denise Brentan; Carollo, Carlos Alexandre

doi:10.1002/pca.3041

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Terpenoids are a diverse class of natural products containing approximately 40,000 known compounds, many of which possess favorable activities and are widely used in various fields such as medicine, food, and cosmetics (Hu et al 2017 ; Bohlmann and Keeling 2008 ). However, traditional methods of plant extraction are time-consuming, labor-intensive, and limited by plant growth (Lu et al 2012 ; Sousa et al 2005 ; Kato et al 2021 ). In recent years, with the rapid development of synthetic biology, efficient production of high-value terpene products using microbial cell factories has attracted increasing attention.…”

Section: Discussionmentioning

confidence: 99%

Development of a Pichia pastoris cell factory for efficient production of germacrene A: a precursor of β-elemene

Cheng

Zuo

Liu

et al. 2023

Bioresour. Bioprocess.

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Abstractβ-Elemene, an active ingredient found in medicinal plants like turmeric and zedoary, is a sesquiterpene compound with antitumor activity against various cancers. However, its current mode of production through plant extraction suffers from low efficiency and limited natural resources. Recently, there has been an increased interest in establishing microbial cell factories to produce germacrene A, which can be converted to β-elemene by a one-step reaction in vitro. In this study, we constructed an engineered Pichia pastoris cell factory for producing germacrene A. We rerouted the fluxes towards germacrene A biosynthesis through the optimization of the linker sequences between germacrene A synthase (GAS) and farnesyl pyrophosphate synthase (ERG20), overexpression of important pathway genes (i.e., IDI1, tHMG1, and ACS), and multi-copy integration of related expression cassettes. In combination with medium optimization and bioprocess engineering, the final titer of germacrene A in a 1 L fermenter reached 1.9 g/L through fed-batch fermentation. This represents the first report on the production of germacrene A in P. pastoris and demonstrates its advantage in producing terpenoids and other value-added natural products. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Development of a Pichia pastoris cell factory for efficient production of germacrene A: a precursor of β-elemene

Cheng

Zuo

Liu

et al. 2023

Bioresour. Bioprocess.

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show abstract

“…Although chemotherapies are important tools for the treatment of different types of cancer, many of the currently used drugs have low selectivity, different levels of systemic toxicity, and cellular resistance to chemotherapeutic agents [ 10 , 11 ]. Thus, natural molecules arising from plants have played a significant role in the development of new chemotherapeutic agents by having a wide structural variety with antitumor potential [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization and Anticancer Activity of a New Anthraquinone from Senna velutina (Fabaceae)

et al. 2023

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In this study, a novel compound was isolated, identified, and its chemical structure was determined from the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by nuclear magnetic resonance (NMR). Subsequently, their cytotoxic activity was evaluated by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. The apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated by flow cytometry technique. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2′-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2′-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel-28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and Ca2+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed cell death pathways induced by 2′-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2′-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

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“…A enorme maioria dos estudos fitoquímicos em Copaifera relatam seus sesquiterpenos e diterpenos, pouco sendo publicado sobre os triterpenos. Dos estudos com a espécie já foram detectados, na casca, os triterpenos ácido betulínico (também detectado no presente estudo), lupeol(Veiga Jr & Pinto 2006) e acetato de lupeíla(Salatino et al 2020) Kato et al (2021). obtiveram um triterpeno do extrato DCM da folha com fórmula C30H46O3, porém esse não pôde…”

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Constituintes da casca externa de plantas do cerrado e suas atividades biológicas

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Todos sabemos os tempos difíceis em que vivem a educação e a pesquisa. Sabemos as mil barreiras a serem superadas para sermos capazes de criar, aprender e descobrir. Por isso, se há alguém a quem não apenas eu gostaria, mas deveria agradecer são meus pais, Patricia e Valmir. Que sempre valorizaram a educação acima de tudo. Que mesmo após decidir por uma carreira desvalorizada (uma triste realidade), com escassez de emprego e baixa perspectiva de alto ganho monetário, nunca, nem ao menos por um segundo, deixaram de me apoiar. Que me deram todo e qualquer suporte nesses 4 anos de faculdade e mais 3 de mestrado (que infelizmente teve de ser estendido por conta da pandemia), seja monetário, ou aquele "empurrãozinho" quando necessário. Que serviram de exemplo de dedicação e força. Que estiveram presentes em todos os meus momentos importantes. Que me fizeram quem eu sou hoje, sem nunca deixar de acreditar. Por isso e por muito mais que um simples parágrafo e poucas palavras são capazes de descrever, a eles agradeço acima de tudo. Agradeço também à minha família, avô e avós, tias e tios, primas e primos, que sempre se orgulharam de quem eu sou e de quem me esforço para me tornar, especialmente meus irmãos, Luana, Natan e Davi, meus maiores companheiros do dia em que nasci até o momento. Gostaria de agradecer também à professora Maria Luiza por se disponibilizar a orientar esse trabalho, possibilitando sua conclusão apesar das enormes dificuldades decorrentes da pandemia. E se entrarmos na questão da pandemia, não posso deixar de citar duas pessoas extremamente importantes, que me ajudaram de extremo bom grado, principalmente no retorno às atividades presenciais: a técnica Mourisa, por toda a dedicação e empenho diário em sempre melhorar o laboratório e ajudar seus usuários; e a colega de laboratório Dra. Priscila, pela preocupação, companhia e os diversos auxílios que me permitiram superar esse desafio. Também agradeço à profa. Dra. Renata da Universidade Estadual Paulista e sua equipe, e o prof. Dr. Gregório da Universidade de São Paulo pela coleta e identificação do material vegetal. Ao professor Salatino, um exemplo para qualquer um que teve a honra de conhecê-lo. Aos colegas de laboratório pela companhia e várias ajudas, em especial ao Eli, a quem recorri em vários momentos de desespero e me auxiliou no ensaio anti-AChE; ao Lucas, que me ensinou a paixão pelo CG-EM; ao Wilton pela ajuda com o ORAC e ao Leonardo e Fabiana no ensaio antibacteriano. Agradeço aos professores do laboratório prof. Marcelo, profa. Cláudia e profa. Débora, pelas disciplinas e por dividir seus conhecimentos. E aos funcionários do laboratório, Suzi, Aline e Leandro, pela dedicação e apoio.Por fim, agradeço ao Instituto de Biociência (IB-USP) por conceder a infraestrutura para a realização do projeto, e à Capes pelo auxílio financeiro. 2.2.Cromatografia a Gás acoplada a espectrometria de massas (CG-EM) .

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Application of the metabolomics approach to the discovery of active compounds from Brazilian trees against resistant human melanoma cells

Cited by 3 publications

References 45 publications

Development of a Pichia pastoris cell factory for efficient production of germacrene A: a precursor of β-elemene

Development of a Pichia pastoris cell factory for efficient production of germacrene A: a precursor of β-elemene

Structural Characterization and Anticancer Activity of a New Anthraquinone from Senna velutina (Fabaceae)

Constituintes da casca externa de plantas do cerrado e suas atividades biológicas

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