Benzylated dihydrochalcones as a novel therapeutic approach for the treatment of hepatocellular and thyroid carcinoma

Dihydrochalcones represent a class of natural flavonoids that are known for their anti-inflammatory and anti-cancer activities. In this context, the natural benzylated dihydrochalcone MF-15, found in Melodorum fruticosum, showed growth suppression of castration-resistant prostate cancer (CRPC) cells by occupying the DNA-binding domain (DBD) of the androgen receptor (AR). Moreover, it was shown that MF-15 interacts with inflammation-related proteins like 5-lipoxygenase (5-LOX) and 15-LOX. Therefore, the hypothesis is that MF-15 acts as a multi-target drug and thus leads to anti-inflammatory and anti-cancer effects in different cancer types. The aim of the underlying study is to evaluate the effect of MF-15 and derivatives on hepatocellular (HCC) and differentiated thyroid carcinoma (DTC) cell proliferation and cell death. Furthermore, potential synergistic effects of MF-15 and lenvatinib combination therapy on HCC and DTC cells are investigated.

The data so far indicated that MF-15 leads to a concentration-dependent inhibition of cell proliferation in HUH7 (IC₅₀=12.3 µM) and Hep3B (HCC, IC₅₀=4.6 µM) as well as in FTC-133, K1 and TPC-1 (DTC) cells. In addition, we demonstrated that slight modifications in the MF-15 structure lead to an 8-fold increase of activity in cell viability assays. We could also show that combination of MF-15 with lenvatinib in FTC-133 cells caused a synergistic proliferation reduction. Beyond that, caspase 3/7 activity measurements suggested that the tested substances caused apoptosis. To sum up, the results indicated that natural plant dihydrochalcones may be promising new lead compounds for the development of anti-cancer small molecules.

 

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Publication History

Article published online:
16 November 2023