Exploring migrastatic compounds: A mitochondrial approach to inhibit cancer cell migration
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| Year of publication | 2023 |
| Type | Conference abstract |
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| Description | In solid tumors, invasiveness and metastasis are responsible for more than 90% of deaths. Even though cancer treatment is at a high level today, the category of drugs against invasiveness and metastasis is still missing. While the aim of cytostatic treatment is to prevent the growth and division of tumor cells, the goal of migrastatic treatment is to prevent the tumor cells from moving, local invasiveness, and metastasis. The best solution would be a combination of these approaches. Here we introduce new compounds belonging to the group of migrastatics. Pentamethinium salts (PMS) are a group of compounds characterized by fluorescence and variable cytotoxicity depending on the structure of the molecule and can play an important role in influencing the migration potential of tumor cells. Specific fluorescent dyes from the pentamethinium family exhibit exceptional affinity and selectivity for cardiolipin in the inner mitochondrial membrane and have excellent photostability, fluorescence properties, and low phototoxicity. Our previous study revealed the inhibitory effect of PMS on DHODH-dependent respiration, a critical step in pyrimidine synthesis. Here, we present the binding of BCV 141 to mitochondria of cancer cells, the inhibition of OXPHOS and overall ATP production, molecular docking with binding to DHODH and IL-6 receptor, migrastatic potential, and inhibition of metastatic seeding in the lungs of mice. |