Simultaneous and dose dependent melanoma cytotoxic and immune stimulatory activity of betulin

PloS One
Kathrin PfarrHeinfried H Radeke

Abstract

Conventional cytostatic cancer treatments rarely result in the complete eradication of tumor cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established tumors. In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of tumor tissue. Genistein, fingolimod and betulin have already been described as active compounds in different types of cancer. Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different B16 melanoma cell lines to a given extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while genistein and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in comparison to the melanoma cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measu...Continue Reading

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Citations

Oct 19, 2017·International Journal of Oncology·Angela CauniiCristina Dehelean
Apr 5, 2019·Journal of Analytical Methods in Chemistry·Katarzyna BoberStanisław Boryczka
May 26, 2018·International Journal of Molecular Sciences·Dorina CoricovacOvidiu Boruga
Oct 13, 2020·Pharmacology & Therapeutics·Laura MasuelliRoberto Bei
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina Adriana DeheleanIulia Pinzaru
May 27, 2021·BMC Veterinary Research·Joanna MałaczewskaBarbara Kazuń

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Methods Mentioned

BETA
transgenic
FCS
FACS
flow cytometry
ELISA
PCR
fluorescence cytometry
dot blots

Software Mentioned

Prism
Quantity One
Flow Jo soft
Graph Pad Prism

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