Cancer Cell Targeting

Solute Carriers (SLCs) as well as ATP-binding cassette (ABC) transporters, so-called efflux transporters are over-expressed in many different types of cancer cells and in solid tumors. Thus, SLCs can be utilized for cancer cell-targeted selective drug delivery or to inhibit and starve the cancer cell from essential nutrients. ABC transporters, on the other hand, have a crucial role in cancer biology and more importantly in chemoresistance, as they can pump a wide range of chemotherapeutics out of the cancer cells and thereby reduce the efficacy of these anti-cancer drugs. Therefore, modulating selectively efflux transporters’ expression and/or may offer a potential alternative to improve the efficacy of chemotherapeutics.

The main aim of our research group is to study:
1. SLCs, such as LAT1, as Selective Carriers of Chemotherapeutics
2. Modulation of ABC Expression/Function via Cancer Cell-Targeted Agents
3. Inhibition SLCs to Prevent Cancer Cell Proliferation

Selected Publications

1. LAT1-Utilizing Prodrugs of Chemotherapeutics or Efflux Transporter Inhibitors

Huttunen, J.; Tampio, J.; Järvinen, J.; Montaser, A.B.; Markowicz-Piasecka, M.; Huttunen, K. M. Amino Acid Derivative of Probenecid Potentiates Apoptosis-Inducing Effects of Vinblastine by Increasing Oxidative Stress in a Cancer Cell-Specific Manner. Chemico-Biological Interactions, 2024, 388: 110833.

Markowicz-Piasecka, M.; Huttunen, J.; Montaser, A.; Adla. S. K.; Auriola, S.; Lehtonen, M.; Huttunen K M. Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP). International Journal of Molecular Sciences, 2021, 22(14): 7727.

Montaser, A.; Markowicz-Piasecka, M.; Sikora, J.; Jalkanen, J.; Huttunen, K. M. L-Type Amino acid Transporter 1 (LAT1)-Utilizing Efflux Transporter Inhibitors Can Improve the Brain Uptake and Apoptosis-Inducing Effects of Vinblastine in Cancer Cells. International Journal of Pharmaceutics, 2020, 586, 119585.

Huttunen J.; Gynther, M.; Huttunen, K. M. Targeted Efflux Transporter Inhibitors – A Solution to Improve Poor Cellular Accumulation of Anti-cancer Agents. International Journal of Pharmaceutics, 2018, 550, 278-289.

2. Other Transporters as Novel Anti-Cancer Carriers 

Markowicz-Piasecka, M.; Huttunen, J.; Zajda, A.; Sikora, J.; Huttunen, K. M. Metformin Derivatives Induce Mitochondrial-Associated Apoptosis and Cell Cycle Arrest in Breast Cancer Cells. Chemico-Biological Interactions, 2022, 352, 109795.

Markowicz-Piasecka, M.; Sadowski, K.; Huttunen, J.; Sikora, J.; Huttunen, K.M. Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells. International Journal of Molecular Sciences, 2021, 22(11): 5642.

Markowicz-Piasecka, M.; Komeil, I.; Huttunen, J.; Sikora, J.; Huttunen, K. M. Effective cellular transport of ortho-halogenated sulfonamide derivatives of metformin is related with improved antiproliferative activity and apoptosis induction in MCF-7 cells. International Journal of Molecular Sciences, 2020, 21, 2389-2417.

Markowicz-Piasecka M, Huttunen J, Sikora J, Huttunen KM. Sulfenamide derivatives can improve transporter-mediated cellular uptake of metformin and induce cytotoxicity in human breast adenocarcinoma cell lines. Bioorganic Chemistry, 2019, 87, 321-334.

3. Inhibitors of LAT1 as a Novel Anti-Cancer Agents

Huttunen, K. M.; Gynther, M.; Huttunen, J.; Puris, E.; Spicer, J. A.; Denny, W. A. A Selective and Slowly Reversible Inhibitor of L-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. Journal of Medicinal Chemistry, 2016, 59 (12), 5740-5751.

Markowicz-Piasecka, M.; Huttunen, J.; Montaser, A.; Huttunen, K. M.  Hemocompatible LAT1-inhibitor Can Induce Apoptosis in Cancer Cells Without Affecting Brain Amino Acid Homeostasis. Apoptosis, 2020, 25(5), 426-440.