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. Selected SLCs, such as LAT1, as Selective Carriers of Chemotherapeutics
2. Modulation of ABC Expression/Function via Cancer Cell-Targeted Agents
3. Inhibition of SLCs to Prevent Cancer Cell Proliferation

 

Selected Publications

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

 

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. https://doi.org/10.3390/ijms22147727 

 

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. https://doi.org/10.1016/j.ijpharm.2020.119585

 

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. https://doi.org/10.1016/j.ijpharm.2018.08.047

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. https://doi.org/10.1016/j.cbi.2021.109795 

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. https://doi.org/10.3390/ijms22115642  

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. https://doi.org/10.1016/j.bioorg.2019.03.036  

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. http://doi.org/10.1016/j.bioorg.2019.03.036

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. http://doi.org/10.1021/acs.jmedchem.6b00190

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. http://doi.org/10.1007/s10495-020-01603-7