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[This corrects the article DOI: 10.18632/oncotarget.28068.].
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Triple-negative breast cancer (TNBC) constitutes a very aggressive type of breast cancer with few options of cytotoxic chemotherapy available for them. A chemotherapy regimen comprising of doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel, known as AC-T, is approved for usage as an adjuvant treatment for this type of breast cancer. In this study we aimed to elucidate the role of KIF11 in TNBC progression throughout its inhibition by two synthetic small molecules containing the DHPM core (dihydropyrimidin-2(1H)-ones or -thiones), with the hypothesis that these inhibitors could be an interesting option of antimitotic drug used alone or as adjuvant therapy in association with AC. For this purpose, we evaluated the efficacy of DHPMs used as monotherapy or in combination with doxorubicin and cyclophosphamide, in Balbc-nude mice bearing breast cancer induced by MDA-MB-231, having AC-T as positive control. Our data provide extensive evidence to demonstrate that KIF11 inhibitors showed pronounced antitumor activity, acting in key points of tumorigenesis and cancer progression in in vivo xenograft model of triple negative breast cancer, like down-regulation of KIF11 and ALDH1-A1. Moreover, they didn't show the classic peripheral neuropathy characterized by impaired mobility, as it is common with paclitaxel use. These results suggest that the use of a MAP inhibitor in breast cancer regimen treatment could be a promising strategy to keep antitumoral activity reducing the side effects.
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Prostatic cancer (PC) stands out in terms of its occurrence, pathophysiology, and unfavorable prognostics in humans and dogs. Natural drugs bear an integrative potential for conventional antineoplastic treatments. In this context, the bioproducts of Synadenium grantii have been empirically used in different parts of Brazil for the integrative treatment of prostate cancer in humans. However, there is no availability of scientific evidence of the antitumor effects of S. grantii. Therefore, this study aimed to investigate the bioactive compounds in the latex of S. grantii using the high-resolution mass spectrophotometry (HRMS) and to evaluate its cytotoxic effects on primary canine PC cell cultures. Four fragments of phorbol ester were identified as potential bioactive compounds using the HRMS. With the help of an MTT ([3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyltetrazolium bromide]) assay, two canine prostatic carcinoma cell lines (PC 1 and PC2) showed a decrease in the tumor cell count, with an Inhibitory concentration 50 (IC50)of 0.8469 and 0.6068 mg/ml, respectively, for PC1 and PC2. In conclusion, the latex of S. grantii contains phorbol esters in its composition, and its aqueous solution has a cytotoxic effect on canine metastatic PC cells in vitro.
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Psidium myrsinites DC. is species known as "araçá", from the Cerrado (savanna) biome in Brazil. It is commonly used as a medicinal plant in the treatment of diarrhea because of its astringent properties. The aims of this study were to carry out phytochemical screening with an exploratory purpose; to investigate toxicity by brine shrimp (Artemia salina) lethality bioassay; and to evaluate antimicrobial activity against Gram-positive and Gram-negative bacteria by determining the minimum inhibitory concentration of the essential oil, acetonic and ethanolic crude extracts, and the fractions obtained with organic solvents of Psidium myrsinites DC. leaves. The phytochemical profile determined the major classes of secondary metabolites present as phenolic compounds (tannins, coumarins, flavonoids, anthraquinone glycosides and terpene compounds). The essential oil and hexane fraction demonstrated a level of strong and mild toxicity respectively, thus encouraging further research with isolated substances from them. The crude ethanolic and acetonic extracts, and hexane fractions, chloroform intermediary, ethyl acetate and aqueous fraction from crude acetonic extract showed the best inhibitory effect on bacterial growth of Gram-positive bacteria with minimum inhibitory concentrations ranging between 62.5 and 250 µg.mL-1. However, the presence of secondary compounds such as tannins, flavonoids and terpenes is probably associated with the inhibitory effect on tested microorganisms, which could justify the medicinal use of the leaves of this species.
Psidium myrsinites DC. é uma espécie do bioma Cerrado conhecida como "araçá" comumente utilizada como planta medicinal no tratamento de diarreias e na cicatrização devido as suas propriedades adstringentes. O objetivo deste trabalho foi realizar a triagem fitoquímica com propósito exploratório e a investigação da toxicidade pelo teste de letalidade em Artemia salina e da atividade antimicrobiana contra bactérias Gram-positivas e Gram-negativas pela determinação da concentração mínima inibitória do óleo essencial, dos extratos brutos acetônico e etanólico, além das frações obtidas com solventes orgânicos de polaridade crescente: hexano, clorofórmio, acetato de etila das folhas de Psidium myrsinites DC. O perfil fitoquímico determinou as principais classes de metabólitos secundários presentes como compostos fenólicos (taninos, cumarinas, flavonoides, heterosídeos antraquinônicos e compostos terpênicos. O óleo essencial e a fração hexano demonstraram nível de toxicidade forte e moderado respectivamente, incentivando assim novas pesquisas com substâncias isoladas dos mesmos. Os extratos brutos etanólico e acetônico, e as frações hexano, intermediária de clorofórmio, acetato de etila e fração aquosa do extrato bruto acetônico demonstraram melhor ação inibitória sobre o crescimento bacteriano de bactérias Gram-positivas com concentrações mínimas inibitórias variando entre 62,5 e 250 µg.mL-1. Contudo, a presença de compostos secundários tais como, taninos, flavonoides e terpenos, provavelmente, está associada ao efeito inibitório sobre os micro-organismos testados, o que poderia justificar o uso medicinal das folhas dessa espécie.