of food-based molecules
of food-based molecules
According to a number of epidemiological studies, high consumption of plant-based foods decreases the risk of cancer because they contain high concentrations of chemopreventive phytochemicals such as polyphenols. These compounds interfere with processes involved in cancer progression, including tumor cell growth, and survival, metastasis, and angiogenesis.
A key focus of our research is to characterize the antitumor and antiangiogenic potential of several molecules naturally present in food that we ingest daily. To date, we have identified four main families of food-based molecules presenting significant cancer-fighting potential:
IN GREEN TEA
IN CRUCIFERS SUCH AS BROCCOLI
IN STRAWBERRIES AND RASPBERRIES
However, recent studies have also shown that molecules present in many other plants demonstrate strong anticancer activity. For example, when comparing the anticancer potential of several commonly consumed vegetables in Quebec, we discovered that the Allium family (garlic, onions, leek) as well as crucifers (cauliflower, cabbage, etc.) significantly inhibit the growth of cancer cells derived from various types of tumors. Similarly, we also observed the tremendous anticancer potential of many berries on a number of very aggressive cancer cell lines. Furthermore, herbs such as parsley and thyme also contain high concentrations of cancer-preventing molecules that interfere with the recruitment of smooth muscle cells involved in the stabilization of new tumor blood vessels. Flavonols, which are found in abundant quantity in many fruits and vegetables, also exhibit anticancer properties. Finally, we observed that curcumin (the principal pigment of turmeric) inhibits tumor growth and angiogenesis in glioblastoma xenografts.
We also examined the relationship between chronic inflammation and the development of certain cancers. Our studies have shown that some polyphenols inhibit tumour angiogenesis and the invasion mechanism of tumour cells, both of which are induced by IL-6, a proinflammatory cytokine. We also reported the effect of lupeol (a compound found in mangoes, olives and figs), resveratrol (found in red wine, grapes and blackberries), luteolin (found in green peppers, parsley, celery, thyme, broccoli and cabbage) on inflammation biomarkers in brain tumors.
Science discovered years ago that the eating habits of people living around the Mediterranean Sea had a positive impact on health, including the prevention of cardiovascular diseases and several types of cancer. Although the molecular mechanisms involved in the protective effect of the Mediterranean diet remain largely unknown, many studies suggest that the omnipresence of olive oil plays an essential part in its protective effect. In addition to its monounsaturated fatty acid content, olive oil also incorporates several powerful antioxidant phenolic compounds that are not found in other vegetable oils. We recently demonstrated that polyphenols and fatty acids found in extra virgin olive oil have antiangiogenic properties.
Together, these results highlight the anticancer properties of food-based compounds and clearly substantiate their influence as prophylactic and therapeutic agents.
Effects of phytochemicals on tumor growth
The key challenge to developing an effective cancer treatment is the ability of cancer cells to stimulate the growth of new blood vessels from existing blood vessels. The newly formed vessels carry oxygen and nutrients that fuel tumor growth, while eliminating metabolic waste and facilitating the spread of cancer cells to other distant organs (metastasis). Angiogenesis results from the production of signaling chemicals such as various cytokines and growth factors which attract nearby blood vessel cells (endothelial cells) in order to build a new capillary network. However, their vasculature differs from normal blood vessels. Accordingly, tumor-based angiogenesis must be prevented, while allowing vessel normalization.
The objective of this project is to characterize antiangiogenic properties of phytochemicals with respect to various key stages of tumor angiogenesis such as cell migration and proliferation, tubulogenesis, metalloproteinase expression, angiogenic receptor activation, etc.
Efficacy of phytochemicals under hypoxic conditions
When a tumor lacks oxygen (hypoxia), it can trigger free radicals leading to tumor cell dysfunction and death. Hypoxia is a major component of tumor progression because it stimulates the formation of blood vessels (angiogenesis) that will feed the tumor. In turn, the tumor can induce the transcription of the hypoxia-inducible factor (HIF) which promotes many genes involved in angiogenesis. Hypoxia helps tumors modulate their response to treatment (radiotherapy, chemical agents), exert selective pressure and modulate angiogenesis, a key factor of metastatic potential.
The objective of this project is to assess in vitro the effect of phytochemicals on angiogenesis in a hypoxic environment in order to develop new therapeutic strategies targeting the tumor microenvironment.
Using phytochemicals to fight tumor-promoting inflammation
There is a strong connection between chronic inflammation and the development of certain types of cancer because inflamed tissues offer an ideal microenvironment with many elements that help cancer cells thrive. When inflammation is chronic, cells from the immune system produce various molecules that ultimately inflict serious damages. As a result, free radicals trigger cellular disruption, while inflammatory cells (leukocytes, lymphocytes, macrophages) that usually respond to aggressions begin facilitating tumor angiogenesis, survival, growth and propagation.
The objective of this project is to study the effect of phytochemicals on proinflammatory cytokines (interleukine-1, tumour necrosis factor) in the development of brain, breast, ovary and colon tumors, and on inflammation biomarkers such as cyclooxygenase-2.
Using phytochemicals to block inflammation and angiogenesis in obesity-related cancers
There is mounting evidence that obesity is involved in a number of cancers. As an endocrine gland, fatty tissue synthesizes hormones called adipokines. An imbalance in these bioactive peptides can be correlated to an increase in tumor angiogenesis which then fuels potentially cancerous cells. Obese people must often deal with a moderate chronic inflammation syndrome that triggers a hypersecretion of proinflammatory cytokines by adipocytes and macrophages, thereby fostering a favorable environment for tumors.
The objective of this project is to study the effect of phytochemicals, such as food-based polyphenols, on adipokines and cytokines secreted by adipocytes (fat cells) in the inflammatory and angiogenic process.
Phytochemicals against epithelial to mesenchymal transition in the development of metastasis
Epithelial to mesenchymal transition (EMT) plays a key role in a tumor’s ability to evolve, especially in the acquisition of metastatic potential during which neoplastic cells develop mesenchymal properties. During EMT, cancer cells drop their adhesive properties while developing migrating and proteolytic characteristics in order to metastasize. The Transforming Growth Factor-β (TGF-β) is a powerful EMT inducer that is over-expressed in all types of cancers. In addition, TGF-β inhibits immune surveillance of the growing tumor. Glioblastomas represent the most common and severe form of primary brain tumor. Patients with this pathology have a very bleak prognosis due to its extremely invasive potential and resistance to chemotherapy. The invasion of normal adjacent brain cells by cancer cells is characteristic of mesenchymal properties of glioblastomas and a key contributing factor to their poor clinical prognosis. Consequently, we need to have a better clinical understanding of the mechanisms regulating EMT in glioblastomas. Despite the well-known role of TGF-b in tumor progression, the impact of diet on its biological activity remains poorly understood.
The objective of this project is to antagonize EMT in glioblastoma cells using food-based polyphenols. We aim to study the role of certain phytochemicals on TGF-β-induced EMT and understand their basic mechanism. The results will provide key insight into the role of diet in the progression of brain tumors.
Exploring the chemopreventive potential of berry cultivars
Berries are packed with phytochemicals (or polyphenols) with anticancer properties that reduce the risk of developing many types of cancer. In our laboratories, we demonstrated that, in addition to their antioxidant potential, phenolic compounds such as ellagic acid in raspberries and anthocyanidins in blueberries can prevent the formation of blood vessels in tumors.
The objective of this project is to study the impact of berries and related phytochemical molecules on the prevention of cancer. For example, we will characterize elderberry (Sambucus canadensis) fruit and flower extracts to assess their anticancer, antiangiogenic and anti-inflammatory potential.