Abstract
This study examined the phytochemical composition, antioxidant efficacy, and cytotoxic properties of Mitragyna speciosa (kratom) extracts and its principal alkaloid, mitragynine. The extracts exhibited significant antioxidant properties, and chemical analysis verified mitragynine as the principal alkaloid, aligning with the distinctive phytochemical profile of M. speciosa. In vitro cytotoxicity studies demonstrated that both kratom extract and mitragynine suppressed cancer cell proliferation (A549, KKU213C, and HeLa cancer cell lines) in a concentration- and time-dependent manner, with mitragynine displaying greater potency compared to the crude extract, especially against cholangiocarcinoma cells. Importantly, synergistic cytotoxic effects were noted when kratom extract or mitragynine was combined with standard chemotherapeutic agents across various cancer cell lines, especially HeLa cervical cancer. These effects correlated with diminished expression of the anti-apoptotic protein BCL-2. In general, the results show that M. speciosa extract and mitragynine are chemosensitizers that could make standard chemotherapy work better. Additional research is necessary to clarify the molecular mechanisms involved and to confirm these effects in vivo. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-43711-5.