Rosane Borges Dias

Antitumour Activity of the Microencapsulation of Annona vepretorum Essential Oil

Annona vepretorum Mart. (Annonaceae), popularly known as ‘bruteira’, has nutritional and medicinal uses. This study investigated the chemical composition and antitumour potential of the essential oil of A. vepretorum leaf alone and complexed with β‐cyclodextrin in a microencapsulation. The essential oil was obtained by hydrodistillation using a Clevenger‐type apparatus and analysed using GC‐MS and GC‐FID. In vitro cytotoxicity of the essential oil and some of its major constituents in tumour cell lines from different histotypes was evaluated using the alamar blue assay. Furthermore, the in vivo efficacy of essential oil was demonstrated in mice inoculated with B16‐F10 mouse melanoma. The essential oil included bicyclogermacrene (35.71%), spathulenol (18.89%), (E)‐β‐ocimene (12.46%), α‐phellandrene (8.08%), o‐cymene (6.24%), germacrene D (3.27%) and α‐pinene (2.18%) as major constituents. The essential oil and spathulenol exhibited promising cytotoxicity. In vivo tumour growth was inhibited by the treatment with the essential oil (inhibition of 34.46%). Importantly, microencapsulation of the essential oil increased in vivo tumour growth inhibition (inhibition of 62.66%).

Anti-liver cancer activity in vitro and in vivo induced by 2-pyridyl 2,3-thiazole derivatives

&NA; A total of 24 hybrid compounds containing pyridyl and 1,3‐thiazole moieties were screened against HL‐60 (leukemia), MCF‐7 (breast adenocarcinoma), HepG2 (hepatocellular carcinoma), NCI‐H292 (lung carcinoma) human tumor cell lines and non‐tumor cells (PBMC, human peripheral blood mononuclear cells). Most of them were highly potent in at least one cell line tested (IC50 ≤ 3 &mgr;M), being HL‐60 the most sensitive and HepG2 the most resistant cell line. Among them, TAP‐07 and TP‐07 presented cytotoxic activity in all tumor cell lines, including HepG2 (IC50 2.2 and 5.6 &mgr;M, respectively) without antiproliferative effects to normal cells (PBMC) (IC50 > 30 &mgr;M), making TAP‐07 and TP‐07, the compounds with the most favorable selectivity index. TAP‐07 and TP‐07 induced apoptosis in HepG2 cells and presented in vivo antitumor activity in hepatocellular xenograft cancer model in C.B‐17 severe combined immunodeficient mice. Systemic toxicological verified by biochemical and histopathological techniques reveled no major signs of toxicity after treatment with TAP‐07 and TP‐07. Together the results indicated the anti‐liver cancer activity of 2‐pyridyl 2,3‐thiazole derivatives. Highlights2‐Pyridyl 2,3‐thiazole derivatives induce selective cytotoxicity to cancer cell lines.2‐Pyridyl 2,3‐thiazole derivatives cause cell death by apoptosis in HepG2 cells.2‐Pyridyl 2,3‐thiazole derivatives inhibit the progression of xenograft HepG2 liver cancer in SCID mice.2‐Pyridyl 2,3‐thiazole derivatives present no major signs of toxicity.

β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells

Abstract &bgr;‐Lapachone is a natural naphthoquinone originally obtained from the bark of the purple Ipe (Tabebuia avellanedae Lor, Bignoniaceae) and its therapeutic potential in human cancer cells has been evaluated in several studies. In this study, we examined the effects of &bgr;‐lapachone and its 3‐iodine derivatives (3‐I‐&agr;‐lapachone and 3‐I‐&bgr;‐lapachone) on cell proliferation, cell death, and cancer‐related gene expression in human oral squamous cell carcinoma cells. &bgr;‐Lapachone and its 3‐iodine derivatives showed potent cytotoxicity against different types of human cancer cell lines. Indeed, treatment with these compounds induced cell cycle arrest at G2/M phase, followed by internucleosomal DNA fragmentation, and caused significant increases in phosphatidylserine externalization, caspase‐8 and ‐9 activation, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, and apoptotic cell death morphology. The apoptosis induced by the compounds was prevented by pretreatment with a pan‐caspase inhibitor (Z‐VAD‐FMK) and an antioxidant (N‐acetyl‐l‐cysteine). In vivo, &bgr;‐lapachone and its 3‐iodine derivatives significantly reduced tumor burden and did not alter any of the biochemical, hematological, or histological parameters of the animals. Overall, &bgr;‐lapachone and its 3‐iodine derivatives showed promising cytotoxic activity due to their ability to induce cell cycle arrest at G2/M phase and promote caspase‐ and ROS‐mediated apoptosis. In addition, &bgr;‐lapachone and its 3‐iodine derivatives were able to suppress tumor growth in vivo, indicating that these compounds may be new antitumor drug candidates. Graphical abstract Figure. No caption available. Highlights&bgr;‐Lapachone and its 3‐iodine derivatives induce apoptosis in human OSCC cells.&bgr;‐Lapachone and its 3‐iodine derivatives increase ROS levels in human OSCC cells.&bgr;‐Lapachone and its 3‐iodine derivatives reduce cell growth in a xenograft model.

Association Between Radiographic Features and Cell Proliferation in Keratocystic Odontogenic Tumor

The radiographic features of an intraosseous lesion are usually associated with the biological behavior of the tumor. In view of the fact that the growth and behavior of keratocystic odontogenic tumors (KCOT) is mainly associated with the proliferation of the cystic epithelium, the objective of the present study was to evaluate the relationship between cell proliferation markers and radiographic features of this tumor. Thirty-seven radiographs of KCOT obtained from 30 patients were scanned and evaluated on a monitor. Sections were submitted to immunohistochemistry for Ki-67, p63, and p53 proteins on an EnVisiona system. Thirty-one KCOTs were observed in the posterior of the mandible, and the unilocular aspect was predominant (n= 26). Nineteen KCOTs distorted the mandibular canal and 11 displaced teeth. Satellite cysts were associated with a multilocular aspect (P= 0.016). p53 was in KCOTS with diffuse margins (p=0.049), p63 with NBCCS (p=0.049) KOT and higher KI-67 positive cells was observed in KCOTs presenting distortion of the mandibular canal (p=0.042). The distribution of Ki-67, p63, and p53 positive cells was similar between KCOTs with uni- and multilocular aspects. The results of the present study suggest that cell proliferation in KCOT contributes to the radiographic features of this tumor.

Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: A preliminary study

BACKGROUND Glypican-3 is a cell surface proteoglycan that is found in embrionary tissues, and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was to investigate glypican-3 in a series of aggressive and non-aggressive odontogenic tumors. METHODS Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, 28 KOTs including five associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry. RESULTS Glypican-3 was observed in seven solid ameloblastoma and eighteen keratocystic odontogenic tumors including three of the five syndromic cases, but there was no significant difference between syndromic and sporadic cases (P > 0.05; Fishers exact Test). All cases of unicystic ameloblastoma (n = 4), adenomatoid odontogenic tumor (n = 5), and calcifying cystic odontogenic tumor (n = 2) were negative. CONCLUSIONS This provided insights into the presence of glypican-3 in odontogenic tumors. This protein distinguished aggressive from non-aggressive odontogenic tumors.

Principles of Cancer Pathogenesis and Therapies: A Brief Overview

Cancer is a group of complex genetic diseases characterized by the uncontrolled growth and spread of abnormal and proliferating cells that have undergone a plethora of changes in multiple genes. In this chapter, we provide an overview of cancer pathogenesis and therapies. In short, scientific and technological advances in all areas of oncology enable earlier and more accurate diagnoses, which improve treatment in cancer patients. Moreover, new classes of anticancer agents have contributed to improved cancer therapies. In this context, natural products are among the most effective cancer chemotherapeutics currently available. The prevention of new cases of cancer and the increased survival and improved quality of life of people with cancer are the current challenges for oncology research.