The Effect of 1-Methyl Propyl 2-Imidazolyl Disulfide (PX-12) on the Invadopodia Formation of Hypoxia-Induced HCT116 Colorectal CancerCells.

Muhammad Shan, Sharah (2022) The Effect of 1-Methyl Propyl 2-Imidazolyl Disulfide (PX-12) on the Invadopodia Formation of Hypoxia-Induced HCT116 Colorectal CancerCells. [Project Paper] (Submitted)

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Abstract

Colorectal cancer is one of the most common solid tumour in both women and men reported by The American Cancer Society. It is the second most common cause of cancer deathsglobally in 2020. Cancer metastasis is a multi-step process that includes the local infiltrations ofcancer cells into the adjacent tissues, migration of cancer cells into the vessels system known asintravasation, followed by extravasation and lastly colonization of secondary sites. Extravasationprocess is the key role in cancer metastasis that allow cancer cells to migrate and invade via protrusive structures known as invadopodia. The ability of invadopodia to degrade extracellular matrix allows the migration of primary tumour to secondary sites. Several studies have evaluated therole of 1-methylpropyl 2-imidazolyl disulfide (PX-12), a thioredoxin inhibitory drug on cancer migration and invasion under normoxic condition, however, little is known on the effects of PX-12 on tumour cell invasion and invadopodia formation in colorectal cancer cells under hypoxic condition. Objective: This study aims to evaluate the cytotoxic effects and invadopodia formation of PX-12 in HCT116 human colorectal cancer cells in normoxic and hypoxic conditions. Hypothesis: It is hypothesised that PX-12 may significantly reduce invadopodia formation of HCT116 colorectal cancer cells under hypoxia condition. Methodology: HCT116 cells were seeded into 96-well plate prior to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay in order to determine the inhibitory concentrations of PX-12. For gelatin degradation assay, HCT116 cells were treated with IC20 of PX-12 for both normoxic and hypoxic conditions and the cells were re-seeded onto gelatin-coated coverslips followed by staining with Rhodamine to observe the invadopodia formation. Results and Discussion: The IC20 values of PX-12 for HCT116 cells at 24 and 48 hours were ranging from 1.5µM to 4µM while the IC50 values ranging from 11µM to 14µM in normoxic and hypoxic conditions. The gelatin degradation assay showed that PX12 at IC20 concentration significantly reduced the number ofcells with invadopodia suggesting that low concentrations of PX-12 (1.5µM to 4µM) were sufficient to reduce colorectal cancer cells invasion. Conclusion: This study suggests that PX-12 can potentially be an anti-invasive drug candidate in colorectal cancer.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 06:49
Last Modified:	22 Aug 2023 06:49
URI:	http://psaspb.upm.edu.my/id/eprint/1359

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