Anticancer potential of limonoids from Swietenia macrophylla: Genotoxic, antiproliferative and proapoptotic effects towards human colorectal cancer.

AIMS: Swietenia macrophylla have been considered for the treatment of various diseases, including anticancer activity. This study aimed to investigate the anticancer activity of S. macrophylla leaves extract and its isolated compound towards human colorectal cancer cell line. MAIN METHODS: Hexanic extract of S. macrophylla leaves demonstrated relevant cytotoxicity only against colon cancer cell line HCT116. KEY FINDINGS: Our results showed significant DNA damage and apoptosis after treatment with the hexanic extract of S. macrophylla. Moreover, no toxicity was noticed for the animal model. The isolated compound limonoid L1 showed potent cytotoxicity against cancer cell lines with IC50 at 55.87 µg mL-1. Limonoid L1 did not trigger any cell membrane rupture in the mice erythrocytes suggesting no toxicity. The antiproliferative effect of L1 was confirmed in colorectal cancer cells by clonogenic assay, inducing G2/M arrest, apoptosis, and DNA damage in cancer-type cells. SIGNIFICANCE: L1 reduced BCL2 and increased ATM, CHK2, TP53, ARF, CDK1, CDKN1A, and CASP3 in the colorectal cancer cell line. These findings suggest that limonoid L1 isolated from S. macrophylla can be a promising anticancer agent in managing colorectal cancer.

Composition, antioxidant capacity and cytotoxic activity of Eugenia uniflora L. chemotype-oils from the Amazon.

ETHNOPHARMACOLOGICAL RELEVANCE: Oils and extracts of Eugenia uniflora have been reported as antimicrobial, antifungal, antinociceptive, antiprotozoal, antioxidant and cytotoxic. AIM OF THE STUDY: The oils of five specimens (E1 to E5) that occur in the Brazilian Amazon were extracted, analyzed for their chemical composition, and submitted to antioxidant and cytotoxic assays. MATERIAL AND METHODS: Oils were hydrodistilled, analyzed by GC and GC-MS, and submitted to PCA and HCA analyses. The antioxidant activity of the oils was evaluated by the DPPH radical scavenging and the ß-carotene/linoleic acid assays. Antiproliferative effects of the oils and curzerene were tested against colon (HCT-116), gastric (AGP-01), and melanoma (SKMEL-19) human cancer cell lines and a normal human fibroblast cell line (MRC-5), using MTT assay. RESULTS: Oxygenated sesquiterpenes and sesquiterpene hydrocarbons such as curzerene, selina-1,3,7(11)-trien-2-one, selina-1,3,7(11)-trien-2-one epoxide, germacrene B, caryophyllene oxide, and (E)-caryophyllene were predominant in the oils. PCA and HCA analyses classified the oils samples into four chemotypes. TEAC values of chemotype II (E3 oil, 228.3 ±â€¯19.2 mg TE/mL) and chemotype III (E4 oil, 217.0 ±â€¯23.3 mg TE/mL) displayed significant antioxidant activities. The oils E2 and E4 showed cytotoxic activity against all cell lines tested HCT-116 (IC50 E2:16.26 µg/mL; IC50 E4:9.28 µg/mL), AGP-01, (IC50 E2:12.60 µg/mL; IC50 E4:8.73 µg/mL), SKMEL-19 (IC50 E2:12.20 µg/mL; IC50 E4:15.42 µg/mL), and MRC-5 (IC50 E2:10.27 µg/mL; IC50 E4:14.95 µg/mL). Curzerene showed the more significant activity against melanoma cells (SKMEL-19, IC50:5.17 µM), induced apoptosis at 5.0 µM and 10.0 µM compared to DMSO, exhibiting a decrease in the cell migration at 5.0 µM and 10.0 µM, after 30 h of treatment. CONCLUSION: The curzerene chemotype oil and E. uniflora oils can be indicated as drug candidates for anticancer activity of the lung, colon, stomach, and melanoma, with a real prospect to their subsequent phytotherapeutic development.

Human Papillomavirus Genotype Distribution among Cervical Cancer Patients prior to Brazilian National HPV Immunization Program.

To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16 in PA was higher in younger women (p < 0.05). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions.

Composition and cytotoxic and antioxidant activities of the oil of Piper aequale Vahl.

BACKGROUND: Piper aequale Vahl is a small shrub that grows in the shadow of large trees in the Carajás National Forest, Municipality of Parauapebas, Para state, Brazil. The local people have used the plant against rheumatism and inflammation. METHODS: The essential oil of the aerial parts was extracted and analyzed by GC and GC-MS. The MTT colorimetric assay was used to measuring the cytotoxic activity of the oil against human cancer lines. The determination of antioxidant activity of the oil was conducted by DPPH radical scavenging assay. RESULTS: The main constituents were δ-elemene (18.92 %), ß-pinene (15.56 %), α-pinene (12.57 %), cubebol (7.20 %), ß-atlantol (5.87 %), and bicyclogermacrene (5.51 %), totalizing 65.63 % of the oil. The oil displayed a strong in vitro cytotoxic activity against the human cancer cell lines HCT-116 (colon) and ACP03 (gastric) with IC50values of 8.69 µg/ml and 1.54 µg/ml, respectively. The oil has induced the apoptosis in a gastric cancer cells in all tested concentration (0.75-3.0 µg/ml), after 72 h of treatment, when compared to negative control (p < 0.001). Also, the oil showed a significant antioxidant activity (280.9 ± 22.2 mg TE/ml), when analyzed as Trolox equivalent, and a weak acetylcholinesterase inhibition, with a detection limit of 100 ng, when compared to the physostigmine standard (1.0 ng). CONCLUSION: The higher cell growth inhibition induced by the oil of P. aequale is probably due to its primary terpene compounds, which were previously reported in the proliferation inhibition, in stimulation of apoptosis and induction of cell cycle arrest in malignant cells.

Epidemiological aspects of HCV infection in non-injecting drug users in the Brazilian state of Pará, eastern Amazon.

BACKGROUND: Currently, sharing of drug paraphernalia is the main form of HCV transmission worldwide. In South America, consistent findings indicate that shared sniffing equipment is an important factor in the spread of HCV among non-injecting drug users. Epidemiological data on the status of HCV infection in illicit drug users in the Amazon region are scarce, although reports of clinical cases of hepatitis or pathologies associated with HCV infection in other population groups are numerous. Thereby, this study investigated the prevalence, genotype frequency, and epidemiological factors associated with HCV infection in non-injecting drug users in the state of Pará, eastern Amazon. RESULTS: During 2008-2011, 300 non-injecting drug users attending drug-treatment centers participated in this study. Most non-injecting drug users were male (63.7%). The mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8 - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV-RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%) of HCV have been identified. A multivariate analysis demonstrated that HCV infection was independently associated with the following factors: "age (≥ 35 years)", "tattoos", "use of a needle or syringe sterilized at home", "shared use of drug paraphernalia", "uses drugs for more than 5 years", and "use of drugs everyday". CONCLUSIONS: This study revealed a high prevalence of HCV infection in non-injecting drug users, and most infections are occasioned by genotype 1. Likely, HCV transmission is associated with the tattoos, the use of needle or syringe sterilized at home by people over the age of 35 years, and sharing, time and frequency of use of non-injecting drugs. These findings should serve as an incentive for the establishment of a program of Hepatitis C prevention and control by the local public-health authorities in order to develop effective policies and strategies for contain the spread of HCV infection.

HCV infection among cocaine users in the state of Pará, Brazilian Amazon.

In this study, the prevalence, genotype frequency, and risk factors for HCV infection in 384 cocaine users were determined. One hundred twenty-four (32.3 %) cocaine users had anti-HCV antibodies and 120 (31.3 %) had HCV-RNA. Genotyping results indicated the predominance of genotypes 1 (73.3 %) and 3 (26.7 %). Multivariate analysis showed an association of HCV infection with tattoos, shared use of paraphernalia, daily cocaine use, and a long history of cocaine use. The epidemiological aspects of HCV infection among cocaine users presented here should serve as an incentive for the establishment of a program of hepatitis C prevention and control by the local public-health authorities in the Amazon.