Assessment of the in Vitro Antimelanoma Potential of Lippia microphylla Cham (Verbenaceae) Essential Oil.

Essential oils stand out among natural products for their complex composition, frequently described in the literature with a range of biological effects. This study evaluated the cytotoxic activity against several human cancer cell lines of essential oils extracted from the leaves of Lippia microphylla (EO-LM) Cham. (Verbenaceae). The melanoma cell line SK-MEL-28 was the most sensitive to the EO-LM, presenting an IC50 of 33.38±1.16 µg/mL. Afterward, the effects of EO-LM on the cell cycle, induction of apoptosis, and production of reactive oxygen species (ROS) were evaluated. We stated a significant increase in the sub-G1 population, indicating apoptosis, later confirmed by an increase of SK-MEL-28 cells labeled with Annexin V-FITC and by the formation of apoptotic bodies and membrane blebs, observed by confocal microscopy. Additionally, EO-LM reduced the production of ROS, indicating antioxidant activity. Therefore, EO-LM exhibits anti-melanoma activity in vitro, suggesting its potential as an anticancer agent.

Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06.

BACKGROUND: Acridine compounds have been described as promising anticancer agents. Previous studies showed that (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro. METHODS: MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125-200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC50) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide-PI-staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test. RESULTS: AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC50: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (p < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001). CONCLUSIONS: AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.

Toxicity and Antitumor Activity of a Thiophene-Acridine Hybrid.

The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene-acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 ± 1.03 µM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.

Intrinsic Motivation of Medical Students from a College with Active Methodology in Brazil: a Cross-Sectional Study / Motivação Intrínseca do Estudante de Medicina de uma Faculdade com Metodologia Ativa no Brasil: Estudo Transversal

ABSTRACT A cross-sectional study based on the Self Determination Theory to identify intrinsic motivation in the tutorial group scenario, and its associated factors in 276 medical students from a college in the Northeast of Brazil between October and December 2016. The Intrinsic Motivation Inventory was utilized following its adaptation and cross-cultural translation. Variables studied: age, gender, marital status, financial dependents, number of attempts at the university entrance exam for the medical course, current semester of study, previous undergraduate training, living with parents, choice of course by parental influence or pressure. Uni and multivariate Poisson analysis were carried out to assess the factors associated with intrinsic motivation; p <0.05 was considered as the significance level for statistical purposes. Average motivation score was 3.8, which indicates motivation. In 2 nd , 6 th and 10 th semester medicine students, the final model maintained as the variable associated with intrinsic motivation those who attempted the medical school entrance exam once or twice compared to those who had had three or more attempts (PR = 0.88, 95% CI (0.79-0.97), p = 0.011). In the analyses assessed by semester, in the second semester, students who had prior undergraduate training before medical school compared to those who had not was the remaining variable (PR = 0.92, 95% IC (0.87-0.97), p = 0.005). In the sixth semester, no statistically significant difference was found, and in the tenth semester the variable of those who attempted the medical school entrance exam once or twice remained (PR = 0.65, 95% IC (0.47-0.88), p = 0.006). The students seemed to be motivated in the group tutorial activity. The fewer number of medical school entry exam attempts and having previous undergraduate training were variables that showed association with intrinsic motivation.

RESUMO Estudo transversal baseado na Teoria da Autodeterminação para identificar a motivação intrínseca no cenário do grupo tutorial e seus fatores associados em 276 estudantes de Medicina de uma faculdade do Nordeste do Brasil entre outubro e dezembro de 2016, tendo sido utilizado o Inventário de Motivação Intrínseca, após sua tradução e adaptação transcultural. Variáveis estudadas: idade, sexo, estado civil, dependentes financeiros, número de tentativas no vestibular para ingresso no curso de Medicina, período em curso, graduação anterior, residência com os pais, escolha do curso por influência ou por pressão dos pais. Realizadas análises uni- e multivariada de Poisson para analisar os fatores associados à motivação intrínseca, foi considerado como nível de significância para fins estatísticos o valor p<0,05. O escore médio da motivação foi de 3,8, indicando motivação. Em estudantes do segundo, sexto e décimo períodos do curso de Medicina, permaneceram no modelo final como variável associada à motivação intrínseca aqueles que haviam realizado uma ou duas tentativas no vestibular, quando comparados aos estudantes que tinham realizado três ou mais tentativas (RP=0,88; IC95%(0,79-0,97); p = 0,011). Nas análises discriminadas por período, no segundo período, permaneceram no modelo final os estudantes que possuíam graduação anterior ao curso de Medicina, quando comparados aos que não possuíam (RP=0,92; IC95% (0,87-0,97); p = 0,005). No sexto período, nenhuma diferença estatisticamente significante foi encontrada; e no décimo período, a variável de ter realizado uma ou duas tentativas no vestibular (RP=0,65; IC95% (0,47-0,88); p = 0,006). Os estudantes se mostraram motivados na atividade do grupo tutorial. O menor número de tentativas no vestibular para ingresso no curso de Medicina e possuir graduação anterior foram variáveis que se mostraram associadas à motivação intrínseca.