Abstract
*Corresponding Author: Vikram Gota, MD (vikramgota@gmail.com). #Presenting Author: Amisha Joshi Keywords metastasis mitocurcumin mitochondrial dynamics Background: Despite only 0.01% of tumor cells successfully metastasizing, metastasis accounts for 90% of cancer deaths. Mitochondria have emerged as a promising therapeutic target, as mitochondrial dynamics are linked to key metastasis traits, including motility, invasion, microenvironment modulation, plasticity, and colonization. Mitocurcumin-1 (MiC), a curcumin derivative with two TPP moieties, selectively accumulates in cancer cell mitochondria. By inhibiting TrxR2 and modulating reactive oxygen species (ROS), MiC demonstrates potential anticancer activity. ROS in turn affects mt-dynamics, hence we aim to evaluate whether MiC modulates metastasis in lung cancer. Materials and Methods: A549, H1299, and LLC-1 lung cancer cell lines were studied. IBIDI inserts facilitated wound healing assays, while Boyden chamber assessed migration and invasion (Matrigel coated). Confocal microscopy analyzed mitochondrial and lysosomal structures, and Western blot evaluated protein levels. Frozen cell samples were sent to MedGenome for transcriptome analysis. Nonobese diabetic-severe combined immunodeficiency and C57BL/6 mice will be used for in vivo MiC evaluation. Results: MiC treatment delayed gap closure in wound healing assays and reduced cell migration and invasion in Boyden chamber experiments. Mesenchymal markers such as N-cadherin, vimentin, and Twist were downregulated. Mitochondria exhibited a more rounded structure, with increased colocalization of mitochondria and lysosomes. Transcriptome analysis further revealed modulation of metastasis-related gene expression in MiC-treated cells compared with controls. Conclusion: Lung cancer cells’ ability to migrate and invade reduces upon MiC treatment. MiC downregulates the early metastatic markers. MiC treatment leads to degradation of mitochondria via mitophagy in human nonsmall cell lung cancer cell lines (A549 and H1299). MiC treatment modulates migration-related genes Article published online: 15 December 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India