Natural products targeting the molecular pathology of salivary gland mucoepidermoid carcinoma: A systematic review of In vitro studies.

Mucoepidermoid carcinoma of the salivary glands has limited systemic treatment options, while natural products have the potential to inhibit tumor survival by modulating multiple molecular pathways. This study aims to elucidate the antitumor activity, biological mechanisms, and translational potential of natural products in a preclinical model of mucoepidermoid carcinoma. A systematic review was conducted in accordance with PRISMA and registered with PROSPERO (CRD420261404862). PubMed, Scopus, ProQuest, ScienceDirect, and Taylor & Francis were searched through July 2026 for studies evaluating the effects of natural products on human mucoepidermoid carcinoma cell lines. Eligibility was based on evidence from human MEC cell-line models in vitro; studies with a corresponding in vivo xenograft component were also eligible, with in vivo findings extracted as supportive translational validation. Data on viability, apoptosis, cell cycle, and molecular pathways were synthesized narratively and mechanistically, while xenograft findings were summarized separately where available. Methodological quality was assessed using QUIN and SciRAP. Fourteen in vitro studies met the inclusion criteria, including four that involved xenograft validation. Overall, the interventions impaired viability or proliferation within a cytotoxic range and primarily induced apoptosis, as evidenced by changes in nuclear morphology, increased Annexin V/PI and sub-G1 fractions, mitochondrial membrane depolarization, caspase activation, and PARP cleavage. A cross-study synthesis revealed mechanistic convergence on ERK/MAPK, Mcl-1, XIAP, and STAT3, linking disruption of survival signaling to mitochondrial apoptosis and the caspase execution phase. Mcl-1 was the most frequently identified anti-apoptotic regulator, while autophagy assessed in two studies demonstrated a cytoprotective function. Heterogeneity in compounds, concentrations, cell lines, and measurement methods hinders comparisons of potency among candidates. Natural products exhibit antiproliferative and proapoptotic activity in a mucoepidermoid carcinoma model by targeting several converging survival pathways. These findings support their development as a source of lead compounds.