Thymol and Carvacrol: Molecular Mechanisms, Therapeutic Potential, and Synergy With Conventional Therapies in Cancer Management.

Monoterpenes like thymol and carvacrol are recognized for their anti-inflammatory and anticancer properties, predominantly found in the Lamiaceae family, particularly in Thymus species, but also present in Verbenaceae, Scrophulariaceae, Ranunculaceae, and Apiaceae families. This review explores their anticancer potential, molecular mechanisms, and synergism with other cancer therapies. The data was collected by using several keywords and MeSH terms, and data from Google Scholar, PubMed, Scopus, and Web of Science indicate that thymol and carvacrol modulate key signaling pathways, including MAPK/ERK, PI3K/AKT, Wnt/β-catenin, JAK/STAT, HH/GLI, and NF-κB. They upregulate pro-apoptotic genes (Bax, Bak, Bid, p53, and SIVA) while downregulating anti-apoptotic genes (Bcl-2, Bcl-xL, XIAP, and cIAP1), leading to apoptosis and cell cycle arrest at G0/G1 and G2/M phases. Thymol derivatives, such as 1,2,3-triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression. In lung cancer (LC), they act as SphK1 inhibitors in NSCLC H1299 and A549 cell lines. Additionally, thymol exhibits anti-EGFR activity, while carvacrol modulates the HIF-1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management. In vitro studies confirm their efficacy against multiple cancer cell lines (MCF-7, HT-29, HeLa, PC-3, HepG2, HL-60), while in vivo animal models highlight their antiproliferative and antitumor effects. Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise. However, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application. This review is the first to comprehensively report thymol and carvacrol in a single study, offering new insights into their anticancer potential.