Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise

Abstract

Cancer is a complex disease of multifactorial cause, considered a major public health problem by the World Health Organization (WHO). One of the main causes of morbidity and mortality worldwide. Although treatments have evolved significantly, there is still a constant search for more effective drugs. An important source is Natural Products (PN). An example of this, terpenes demonstrate biological activity against cancer, acting during early tumorigenesis, late carcinogenic stages, invasion phase and metastasis. A terpene that is quite abundant in nature and has demonstrated anticancer activity in in vivo and in vitro studies was limonene. However, the mechanisms of limonene's antitumor activity are not fully understood. The aim of the present study is, therefore, to evaluate the antitumor activity of terpenes and the mechanism of action of limonene in tumor cells. To assess the development of terpenes for antitumor activity, a search for terpene patents or terpene formulations was carried out in specialized databases of the World Intellectual Property Organization (WIPO) and Espacenet. Of the total of the seven patents included in the review, China and Japan were the countries that filed the most, three of them were filed by industry and only one is commercialized. Although there is great scientific interest in terpenes, the industry has invested little in this class of natural cancer products. A systematic review with meta-analysis was used to assess the mechanism of action of limonene in tumor cells through a comprehensive systematic search using the Scopus, MEDLINE-PubMed, Web of Science and Science Direct databases, using the descriptors: "limonene "," cancer "," neoplasm "," tumor ". The risk of bias was assessed and considered high, according to the Risk of Bias tool from SYRCLE (RoB). The mechanism of action used by limonene seems to be the induction of cells to apoptosis mainly by the mitochondrial pathway, and can also activate by other signaling pathways. The meta-analysis suggests that limonene acts mainly in apoptosis induced by tumor regression and is therefore a promising natural product for use in the treatment of various types of cancer.