Plant-derived compounds for pharmacological targeting of death and survival signaling
Plant-derivative compounds and cancer
We have identified a number of compounds that affect the survival signaling of cells in way that will sensitize cancer to cell death. Among these, there are a number of lignan/ AA derivatives that have previously been shown to have antitumor effect. We have now established that this effect is likely due to the inhibitory effect of these compounds on the PI3 kinase-Akt signaling pathway.
Plant lignans sensitize prostate cancer cells to TRAIL-mediated apoptosis. Our group has shown that lignans have the ability to sensitize TRAIL-resistant prostate cancer cells for TRAIL-mediated apoptosis. Our current aims are to characterize the key structural features for their function and to further define their mechanism of action. This and other similar projects aiming at sensitization of cells to apoptotic signaling are going on as technology transfer initiatives (see separate page on Apoptosis).
Anisomelic acid (AA)
Anisomelic acid (AA) is one of the major bioactive compounds found in a medicinal plant, Anisomeles malabarica (L.) R.Br. Recently, our group has revealed the molecular mechanism of AA-mediated apoptosis, demonstrating that AA inhibits expression of the viral E6 and E7 oncoproteins at the protein level. This leads to the activation of the p53-p21 pathway, which effectively results in G2/M cell cycle arrest in HPV-positive cells. Our current aim is to use the molecular action modality of AA as a powerful pharmacological strategy to develop therapies against HPV-mediated cancers, especially cervical cancers, and for prevention of HPV-mediated cancer risk.
Nanoparticles as carriers of antitumor drugs
In a collaborative project on biocompatible nanoparticles, together with the Mika Lindén and Jessica Rosenholm of the FunMat-consortium and Cecilia Sahlgren at the Cell Fate Laboratory at Turku Centre for Biotechnology, we have shown that specific targeting of nanoparticles to cancer cells is possible and, furthermore, that the nanoparticles can be used as carriers for antitumor drugs. The project aims at developing this concept further to get better specificity and to employ the particles also as carriers for other types of compounds.