Umbelliprenin is a member of the 7-prenyloxycoumarins with potential therapeutic properties such as cytotoxic effects on various
cancer cells. The present study investigates the effect of
umbelliprenin on predominance of Th1 and Th2 responses in Lewis
lung cancer (LLC) mouse model. The cytotoxic effect of
umbelliprenin was explored on LLC cells and mouse splenocytes by MTT assay. Mice into which LLC had been transplanted were treated with
umbelliprenin on alternate days, at 2.5 mg/200 µl intraperitoneally. Foxp3, TNF-α and TGF-β
mRNA expressions were assessed in
tumor and lung tissues of LLC mice. In addition,
IL-10, IFN-γ and
IL-4 levels were determined in sera and also in splenocyte culture supernatants at the presence of
tumor cell lysate (10 µg/ml) and Con A (3 µg/ml) after 72 h. Results showed the cytotoxic effects of
umbelliprenin on LLC cells (IC₅₀ = 51.6 ± 5.4 µM) while no adverse effect was seen at this concentration on normal splenocytes. TNF-α
mRNA expression in both lung and
tumor tissues was increased. However, Foxp3 and TGF-β expressions were decreased in
tumor tissues. Serum level of IFN-γ was elevated in the
umbelliprenin treated cancerous mice compared to the control group while
IL-10 and
IL-4 secretions were reduced.
Tumor size was also decreased in
umbelliprenin treated group. In summary,
umbelliprenin has shown a partially Th1 bias with a reduction of regulatory immune response. Although the mechanism behind this action is not known, it is speculated that upon changing the Th1/Th2 balance in favour of Th1,
umbelliprenin induces its antitumor activity.