Isolation, identification and mechanism of action of anticancer active principles of Croton campestris A.St.-Hil.

• Grant number: 11/22457-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2012
• Effective date (End): August 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: João Ernesto de Carvalho
• Grantee: Paula Araujo Monteiro
• Host Institution: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA). Universidade Estadual de Campinas (UNICAMP). Paulínia , SP, Brazil
• Associated scholarship(s): 15/18328-8 - Anti-inflammatory and antitumor activity of active principles from Croton campestris A. St.-Hil: mechanisms of action and links, BE.EP.DR

Abstract

The increase in life expectancy and habits that increase exposure to carcinogens such as tobacco, alcohol and bad diet, have been increasing the incidence of cancer. This is related to the action of carcinogens that favors the appearance of disease. Cancer is the second leading cause of death in the population. Tumor cells are characterized by ignoring the signals that regulate cell proliferation, differentiation process and apoptosis, and present a high capacity for invasion and metastasis. The most chemotherapeutic drugs used in cancer treatment comes from natural sources. The anticancer activity of extracts from the leaves of Croton campestris A.St.-Hil. was initially evaluated by the Division of Pharmacology and Toxicology in project financed by FAPESP (FAPESP-Bioprospecta 2004/07943-9), which executed the screening of 200 extracts species of São Paulo. This plant was evaluated also in a scientific initiation project (FAPESP 2006/61249-2) that compared the anticancer activity of extracts obtained from species popularly used for treatment of parasitic diseases. The results directed the master's project already concluded (FAPESP 2010/02945-4). This study deepened the evaluation and characterized the anticancer activity of extracts and fractions obtained from C. campestris. Potent anticancer activity was observed in cultures of human tumor cells, especially for lung line (NCI-H460), and in in vivo experimental models that presented inhibition of tumor development in mice Ehrlich solid. The work of isolation was guided by the testing activity in cultured tumor cells and identified, so far, the diterpenes velamone and velamolone among the probably anticancer principles. The current project will continue this work in order to isolate and identify active compounds with anticancer activity, and to determine its mechanism of action. In this work we will assessed the cellular pathways involved in the antitumor activity besides we will evaluate other corroborative actions of this activity, as inhibition of angiogenesis and metastatic processes. Extraction, fractionation, isolation and identification of the active principles will be biomonitored through tests in cultured of human tumor cells and normal keratinocyte line. The lines with selectivity for the active principles, as observed for NCI-H460 (lung), will be selected for the study of mechanism of cell death by flow cytometry. We will investigate also the cell death markers such as p53, p21, bcl-2, among others that will enable the assessment of death pathways involved. From the results obtained in cell culture, the active principles will be evaluated in two in vivo experimental models: Ehrlich's solid tumor and through implantation of the semi-permeable fibers (hollow fiber) in mice, containing human tumor cells in order to evaluate the effectiveness of the active principles under metabolic processes. The study is a pioneer for this species and has shown promising results, which confirms its continuity with the long-term goal of providing a new compound for the cancer treatment.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE PAIVA, PAULA P.; NUNES, JULIA H. B.; NONATO, FABIANA R.; RUIZ, ANA L. T. G.; ZAFRED, RAFAEL R. T.; SOUSA, ILZA M. O.; OKUBO, MARCIA Y.; KAWANO, DANIEL F.; MONTEIRO, PAULA A.; FOGLIO, MARY A.; et al. In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained fromBoehmeria caudataSw. Aerial Parts. Molecules, v. 25, n. 17, SEP 2020. (17/21801-2, 12/19661-4, 11/22458-3, 14/06636-7, 11/22457-7)

MONTEIRO, PAULA ARAUJO; MACCARI ZELIOLI, ICARO AUGUSTO; DE OLIVEIRA SOUSA, ILZA MARIA; TASCA GOIS RUIZ, ANA LUCIA; VENDRAMINI-COSTA, DEBORA BARBOSA; FOGLIO, MARY ANN; DE CARVALHO, JOAO ERNESTO. Chemical composition and antiproliferative activity of Croton campestris A.St.-Hil. essential oil. NATURAL PRODUCT RESEARCH, v. 33, n. 4, p. 580-583, FEB 16 2019. (11/22457-7)

DE PAIVA, PAULA P.; NUNES, JULIA H. B.; NONATO, FABIANA R.; RUIZ, ANA L. T. G.; ZAFRED, RAFAEL R. T.; SOUSA, ILZA M. O.; OKUBO, MARCIA Y.; KAWANO, DANIEL F.; MONTEIRO, PAULA A.; FOGLIO, MARY A.; et al. In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained fromBoehmeria caudataSw. Aerial Parts. Molecules, v. 25, n. 17, p. 20-pg., 2020-09-01. (12/19661-4, 17/21801-2, 11/22457-7, 11/22458-3, 14/06636-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MONTEIRO, Paula Araujo. Croton campestris A.St.-Hil.: antitumor and anti-inflammatory activities. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.