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Study focusing on human Sodium-dependent Multivitamin Transporter (hSMVT) and its application in cancer cell targeting

CSEF · 2023 Toxicology Third Award

Ghosh Arjun · 11

Overview

Colon cancer is the third leading cause of cancer related deaths with over 940,000 deaths reported worldwide in 2020. The overexpression of certain membrane bound proteins, such as Sodium-dependent Multivitamin Transporter (SMVT), allow colonic cancer cells to be targeted. My project involves studying the SMVT protein overexpression and designing a biotin cancer drug (temozolomide) conjugate for cancer cell targeting. I studied SMVT regulation using proteasomal (Lactacystin) and lysosomal (Bafilomycin) pathway inhibitors to analyze degradation pathways of SMVT. The results of my experiments show higher SMVT expression after cells were treated with both inhibitors. Since cancer cells often have several mutations which affect proteins, experiments to learn about SMVT functionality in cancer cells were conducted. The results show an increase in biotin uptake after the cells were treated with either inhibitor, indicating that the overexpressed SMVT are functional. Since biotin conjugates have been shown to be transported by SMVT across cell membrane, I created a model for a biotin conjugate using the cancer drug temozolomide. I used protein model Mhp1, homologous to SMVT, and the biotinylated temozolomide to test the docking. I found 5 possible binding sites where the biotinylated conjugate could bind, with the strongest dock having a binding energy of -8.9 kCal/mole. My project provide important insights into SMVT protein expression in the context of drug targeting for cancer therapy. For future work, I plan to extend this project as a framework of drug targeting for other forms of cancer which also express the SMVT protein.

Source coverage

This record comes from a published award list, not a complete project archive. Its abstract comes from CSEF's public project showcase as archived by the Internet Archive before judging (https://web.archive.org/web/20230401224130/https://ca-csef.zfairs.com/showcase/ShowcaseInfo?f=838e60b7-ea75-46e8-865c-fde4864244b3); the version presented may differ.

Awards (2)

Competition history

  • CSEF 2023 Toxicology · Entry S2107

Resources

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