We have been investigating a large number of potential therapeutics for anti-cancer activity in vitro and in mouse models. We made the most progress in testing the efficacy of exposure to a specific electromagnetic field as an anti-cancer treatment. This project was developed in collaboration with Dr Michael Persinger. We have shown that daily exposure to this specific, complex EMF can inhibit cancer cell growth in vitro and in a mouse model. The mechanism underlying this effect involves EMF-dependent alterations in calcium influx, via voltage-gated T channels, which alters cell signaling pathways, cyclin expression, and cell growth. In vivo, exposure to the EMF also seems to promote leukocyte influx into the tumour. We still plan to more completely understand the mechanistic basis of this affect, examine the possibility of synergism with other agents, and develop a clinically testable apparatus.
In addition, we have evaluated several plant extracts for anti-cancer activities. We have shown that treatment of cultured cancer cells with flaxseed oil promotes cellular apoptosis while treatment of non-malignant cultured cells has no significant effect. We characterized some of the fatty acid components of flaxseed oil which appear to be critical for this effect.
We also showed that the South American traditional plant, Uncaria tomentosa (Cat’s claw), can inhibit inflammatory responses in monocytes and can promote apoptosis in some cancer cells. This appears related to the inhibition of the NF-kB transcription factor (subunit p50) in response to treatment with Uncaria extracts. Treatment with Uncaria tomentosa extracts can also inhibit cancer growth in a mouse model.
We also showed that a wide range of natural products or traditional medicines can inhibit cell growth or promote apoptosis in cancer cells. For example, studies looking at Nigella sativa, honey, Andrographis, Zingiber, Chaga mushroom, and Princes pine have been conducted. These projects involved fractionation of the extract to identify active agents (or active combinations) and determining the mechanistic targets of these agents.
● Adhesion-dependent signaling
I studied the effects of integrin-dependent cell adhesion on cell signaling pathways in a variety of cell models since my graduate and postdoctoral studies. We showed that cell adhesion to fibronectin-coated substrates activates a wide range of signaling molecules including PKC, PI 3-kinase, and ERK kinase pathways. We also showed that cell differentiation can be induced by cell adhesion in a process dependent on changes in gene expression and the activation of PKC and MAP kinase signaling pathways. Other work on this project examined the effect of cell adhesion on drug resistance in cancer cells, and on the promotion of pro-inflammatory effectors in immune cells. Further, there appears to be significant “cross-talk” among these signaling pathways which is required to promote changes in cell behaviour in response to cell adhesion.
● Prognostic Biomarkers
Over the last several years we attempted to identify genetic or protein biomarkers that can predict outcome for patients with breast cancer being treated with standard chemotherapies. For example, we have shown that there is an association between single nucleotide polymorphisms in DNA repair and cellular detoxification enzymes and clinical outcome for some patients with breast cancer. We have also shown that immune system markers such as cytokines and immune cell types (imunophenotype) can be associated with responses to therapies. The goal of these studies was to develop a group of prognostic biomarkers that can be used by clinicians to assist choosing the best therapy option.
