Application and effects of metal-based therapeutics on cancer cell lines in tissue culture
Date
2024
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Abstract
In recent years, metal-based drugs have emerged as significant players in the field of therapeutics, leveraging the unique properties of metals to enhance medical treatments. These compounds, incorporating transition metals such as vanadium and platinum, have shown remarkable efficacy in treating various conditions, most notably cancer. The ability of such metals to form complex structures with organic molecules allows for precise targeting and modulation of biological pathways, leading to improved drug efficacy and reduced side effects. Thus, this approach has opened new avenues for designing advanced therapeutics such as vanadium(V) Schiff base catecholate complexes for the treatment of cancer. This thesis aims to explore the potential of non-innocent Schiff base vanadium(V) catecholate complexes as promising agents against glioblastoma, an aggressive form of brain cancer. Two catecholate ligands, 3,5-di-isopropyl catechol and 3,4,6-tri-isopropyl catechol, were synthesized and coordinated to both known and novel vanadium(V) Schiff base scaffolds. Upon testing on glioblastoma T98g cell lines, two of the new complexes, namely [VO(3-tBuHSHED)(TIPCAT)] and [VO(3,5-tBuHSHED)(TIPCAT)], showed remarkable antiproliferative activity. Parallelly, the manuscript delves into the therapeutic applications of platinum-based drugs and how the resistance of platinum-based chemotherapeutics remains a significant challenge. This area of the manuscript identifies the newly discovered role of long non-coding RNAs in platinum-resistance in gastrointestinal cancer treatment. The interaction of these drugs with cellular RNA, in addition to DNA, contributes to this resistance. This manuscript examines the speciation of cisplatin and oxaliplatin, their interactions with DNA and RNA, and the resulting physiological responses of long non-coding RNAs. It identifies aberrantly expressed lncRNAs in platinum-resistant gastrointestinal cancer cell lines, including those from oral cavity, esophageal, gastric, and colorectal cancers. Despite testing different cell lines, similar patterns of aberrant expression compared to normal cells suggest consistent changes in gene expression and cellular pathways. Understanding these changes may help develop new therapeutic strategies for gastrointestinal cancer patients. Together, the vanadium(V) complex investigations and the new insights into platinum-resistance underscore progress in the understanding of the molecular interactions of metal-based drugs, offering pathways to enhance their efficacy and overcome resistance in cancer therapy.
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Embargo expires: 08/16/2025.