Linden (Tilia cordata) as a tool for helping with Cancer (anticancer research)

This study investigated the anti-cancer effects of the chemically characterized Tilia species (linden) on MIA PaCa-2 cells by analyzing various cancer-triggering mechanisms, including oxidative stress and inflammation status. Extracts from the flowers, bracts, and inflorescences of T. cordata, T. platyphyllos, T. rubra, and T. tomentosa were evaluated for antioxidant activity; subsequently, their ability to mitigate inflammation was assessed through in vitro nitrite assays in LPS-induced RAW264.7 cells. The anticancer potentials of the extracts against MIA PaCa-2 pancreatic cancer cells were investigated in 2D (cytotoxic effect) and 3D (effect on spheroid growth) models in vitro. All investigated Tilia species displayed remarkable antioxidant activity and significantly inhibited LPS-induced nitrite, IL-6, and PGE 2 production. Extract from T. rubra bracts showed the highest cytotoxic activity against MIA PaCa-2 cells with an IC 50 value of 0.16 mg/mL, as well as the most significant delay on spheroid growth, which was further confirmed through the arrest in cell cycle. In the Annexin V cell death assays of T. rubra, cells treated with the flower extract exhibited the highest rate of necrotic population with 66.53%. Overall, our results highlight a potential use for Tilia extracts, particularly T. rubra, in pancreatic cancer treatment by modulating cell death.

Tilia species are widely used in Europe as medicinal plants. The selective antiproliferative activity of a Tilia cordata flower dichloromethane extract (DME) on a lymphoma cell line has been reported previously and in order to extend this to other unstudied Tilia species, the effect of Tilia x viridis DME on the proliferation of tumor and normal murine lymphocytes was investigated. The bioguided fractionation of DME yielded a fraction rich in limonene (L), alpha-pinene and beta-pinene, which presented a selective antiproliferative action on tumor lymphocytes (EC(50) on tumor cells: 3.8 +/- 0.2 microg/mL; EC(50) on normal cells: 205 +/- 1.8 microg/mL). While all monoterpenes exhibited this activity, limonene proved to be the most active (EC(50) on tumor cells: 35 +/- 2.0 microg/mL; EC(50) on normal cells: 72 +/- 5.0 microg/mL) also exerting a stimulatory effect on non-mitogen stimulated lymphocytes proliferation (% of stimulation respect to control) (mean +/- SEM): L 10 microg/mL: 25 +/- 1.0%; 20 microg/mL: 38.5 +/- 2.5%; L 40 microg/mL: 41 +/- 0.9%; L 60 microg/mL: 58.5 +/- 3%. T. x viridis may thus constitute a potential source of monoterpenes with immunomodulatory activity.