Role of Phytochemicals in Modulating Signaling Cascades in Cancer Cells

Dietary and environmental factors have been known to affect human health, for good or for bad. Diet plays a crucial role in modulating the disease state in an individual. Among the different chronic diseases, cancer has been the most researched topic due to its wide associations and high mortality rate. Efforts have been made to elucidate molecular mechanisms capable of altering pathways of carcinogenesis. Though chemical drugs have proved their worth as anticancer drugs, the side effects far exceed the benefit they confer. In contrast, plants are considered as the highest source of phytochemicals that offer great potential of acting as an anticarcinogenic agent with minimal side effects. They help in upregulating cytoprotective genes, encoding carcinogenic detoxifying enzymes, and antioxidant enzymes. Higher consumption of berries, vegetables, and whole grains has been associated with reduced cancer risk and other chronic diseases. In general, it has been shown that phytochemicals modulate oncogenic processes by their antioxidant and anti-inflammatory activities and their capacity to replicate the chemical structure and hormone production. Phytochemicals act as anticancer agents that target signaling pathways at different levels, such as transcriptional and post-transcription control, protein activation, and intercellular communication. These compounds have been known to modulate coding as well as non-coding RNAs such as microRNAs and short non-coding RNAs. Other mechanistic pathways for chemoprevention involve the initiation of cell cycle arrest and apoptosis and disruption of signal transduction pathways mainly of mitogen-activated protein kinases, phosphoinositide 3-kinase, protein kinases C, glycogen synthase kinase contributing to pathological cyclooxygenase-2, activator protein-1, nuclear factor kB, and c-myc expression. The Warburg effect is another interesting target for chemotherapeutics. A logical approach for chemoprevention is to address malfunctioning molecules along the compromised signal transduction pathway in cancer. Another crucial chemotherapeutic strategy is to counter the pathways involved in controlling the invasiveness and angiogenesis of tumors. Therefore, cell signaling cascades and their influencing factors have become important targets of chemoprevention, and in this direction the plant extracts are showing promising leads.