Background: Cancer is a complex, multifactorial disease, and a major public health problem, as it is a leading
cause of morbidity and mortality worldwide. Although treatments have significantly improved, there is a still a search for
more effective drugs. One source for these are natural products (NPs). One NP that has shown anticancer activity is
Limonene. However, the mechanisms of limonene's antiproliferative, anticancer and antineoplastic activity are not fully
Objective: The objective of this study is, therefore, to undertake a systematic review and meta-analysis of the literature on
Methods: A comprehensive literature search was performed using the Scopus, MEDLINE-PubMed, Web of Science, and
Science Direct databases using the keywords: "limonene", “cancer”, “neoplasm”, “tumor”. The inclusion criteria were: in
vivo and in vitro studies on the use of limonene in cancer published in English, Portuguese and Spanish until December
2019. Review articles, meta-analyses, abstracts, conference papers, editorials/letters and case reports were excluded.
Results: The search identified 3568 articles. Of which 126 were selected for full reading with 11 papers meeting the review
criteria. Six more papers were added from the references of the initial 11 texts, giving a total of 17 papers. There was a high
level of agreement on inclusion/exclusion (Kappa index > 80%). Risk of bias I the texts was shown to be high.
Conclusion: The meta-analysis suggests that limonene acts mainly on tumor regression induced apoptosis, and is a
promising natural product for use in the treatment of several types of cancer.