Abstract

Abstract Lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide. Cigarette smoke-induced oxidative and inflammatory responses are the major risk factors for the development of lung cancer. Several compounds have been tested for their efficacy in preventing lung cancer. However, very few compounds have gone through clinical studies. We hypothesize that with its potent anti-oxidative and anti-inflammatory actions, fursultiamine, a disulfide lipid-soluble derivative of vitamin B1 (thiamine), could prevent lung cancer growth and spread. Our results indicate that treatment of non-small cell lung cancer cells (A549 cells) with fursultiamine prevents A549 cells death in a dose-dependent manner. Similarly, live and dead cell staining assay also confirms that fursultiamine prevents proliferation of A549 cells. Further, fursultiamine prevents A549 cell proliferation by inducing the apoptotic cell death. It also promoted the activation of caspase-3 and cleavage of PARP protein. Fursultiamine also prevented reactive oxygen species in A549 cells. Further, fursultiamine regulated the expression of various anti-apoptotic (Bcl-2, Bcl-x) and pro-apoptotic (Cleaved Caspase-3), survival (Survivin) and anti-survival factors (Clusterin, p-Rad17) in A549 cells. We next planned to examine the effect of fursultiamine on lung cancer growth in vivo using athymic nude mice injected with A549 cells subcutaneously without or with a diet containing fursultiamine. In conclusion, our in vitro results suggest that vitamin B1 derivative, fursultiamine, by promoting the apoptotic pathways prevents lung cancer growth and has potential for further development as a chemoprevention drug. Citation Format: Noah Boekweg, Ryan Powers, Kota Ramana. Vitamin B1 derivative, fursultiamine, prevents lung cancer cells growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 662.

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