(2020), ChinaHCT116C46.74?g/mL – 48?hLoVo24, 48 and 72?h of incubationBaxCell migration and invasionCaspase-3 and PARPCell cycle stopCells in phase G0/G1Bcl-2Cells in S and G2/M phasesAGS0C600?MCellTiter-Glo Luminescent cell viability assayCytotoxic effectsCell viability75.63 4.01 MC24?hThymol has cytotoxic and antioxidant effects in gastric adenocarcinoma Gnes-Bayir et al. the SYRCLE Risk of Bias tool was used, and for studies, a modified version was used. Results: A total of 1 1,170 records were recognized, with 77 meeting the founded criteria. The studies were published between 2003 and 2021, with 69 becoming and 10 Forty-three used carvacrol, 19 thymol, and 15 studies tested both monoterpenes. It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR). Conclusions: Carvacrol and thymol exhibited antitumor and antiproliferative activity through several signaling pathways. studies with powerful strategy are required to define a standard and safe dose, determine their harmful or side effects, and clarify its precise mechanisms of action. This systematic review was authorized in the PROSPERO database (CRD42020176736) and the protocol is available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176736. Nutt. varieties (Martino et al., 2018). More recently, additional compounds, such as perillyl alcohol and limonene -monoterpenes found in aromatic flower varieties, have been widely analyzed because of the antitumor potential, and have been included in medical phase studies (Shojaei et al., 2014; Arya and Saldanha, 2019). With this context, carvacrol (5-isopropyl-2-methylphenol) and its thymol isomer (2-isopropyl-5-methylphenol), classified as natural multi-target compounds, deserve attention. Both are monoterpenoid phenols, the main parts present in essential oils from several flower varieties of the Lamiaceae and Verbenaceae family members, such as oregano (L.), thyme (and studies of malignancy cell lines, study of animals with malignancy; cytotoxic effect, antitumor effect, inhibition of proliferation and apoptosis and experimental studies (and experimental studies (Hooijmans et al., 2014). We analyzed the following ten domains: sequence generation, allocation concealment and random accommodation (selection bias), random accommodation and concealment (overall performance bias), random evaluation and concealment of results (detection bias), incomplete result data (bias of attrition), selective statement of results (statement bias) and additional sources of SBC-110736 bias, such as inappropriate influence from financiers. An adapted protocol of the SYRCLE Risk of Bias tool was used to evaluate the methodological quality of studies, as explained by Chan et al. (2017). The methodological quality was classified as low, unclear or high, according to the founded criteria (Hooijmans et al., 2014). Statistical Analysis IC50 values identified 24?h after the incubation of the studied cells with carvacrol or thymol were compiled, submitted to the standardization of the unit (M) (Supplementary Table S2) and were expressed while mean standard error of the mean (SEM). Results Study Selection The initial search resulted in 1,170 records, of which 594, SBC-110736 169, 194, and 213 were found in PubMed, Web of Science, Scopus and Lilacs, respectively. Of these, 388 were excluded due to duplication. After screening the title and abstract, 706 reports were excluded, and 1 statement was wanted for retrieval, as it met the criteria after reading the full text, resulting in 77 studies. Of these, three were excluded after reading the full text (two for showing the same results and one that tested the anti-cancer effect on bacteria) and four for not having access to the full text, resulting in 70 articles. In addition, 9 studies were recognized after a manual search of the referrals and two studies from additional sources, but only seven studies were added (two studies were excluded for having a mixture between carvacrol and thymol, one for being associated with additional substances, and one SBC-110736 that studied the draw out of a flower rich in thymol), finally resulting in 77 included studies (Number 1). There was almost perfect (Landis and Koch, 1977) reliability/agreement (= 0.813) among the reviewers, after selecting the titles and abstracts. Open in a separate window Number 1 Flowchart of included studies. Overview of Included Studies The selected studies were carried out in different countries: India (= 14), China (= 14), Turkey (= 13), the Republic of AKAP13 Korea (= 5), Slovakia (= 5), Iran (= 5), Morocco (= 2), Brazil (= 2), Greece (= 2), Iraq (= 2), The United States of America (= 2), Canada (= 2), Egypt (= 2), Croatia (= 1), Lithuania (= 1), Italy (= 1), Spain (= 1), The United Kingdom (= 1), Peru (= 1), Belgium (= 1). Asia (51.9%) was the continent with the largest quantity of publications on the subject, followed by Europe (33.7%), the Americas (9.3%) and Africa (5.1%), with a greater trend of publications on this subject in the last three years.