Choriocarcinoma

Herbal Extracts from Carica papaya and Azadirachta indica: What Role for ROS in Cancer Cell Lines?

The use of plant-derived medications in the treatment and prevention of diseases, i.e., phytotherapy, comprises the traditional knowledge of therapeutic advantages deriving from the use of herbal parts to prevent, protect against and cure several pathologic conditions, such as cancerous, metabolic and inflammatory diseases. Herbal medications are prevalent in countries with limited resources, but, recently, increasing attention is devoted to their exploitation in cancer management on the basis of their low cost and side effects absence compared to conventional radiation or chemotherapic cancer approach. Currently, about 114,000 herbal extracts have screened for anticancer activity and 60% of the commercially available and clinically used cancer drugs, such as vinblastine and vincristine, paclitaxel, campothecin and its derivatives, are from natural sources. These compounds are active against a number of cancer types (ovarian, breast, lung, colon, liver, blood, prostate cancer). There are many types of cancer elicited by several factors that still render this disease a major public health problem, almost everywhere in the world.

The human body is constantly exposed to free radicals arising from exogenous and endogenous origins, which cause oxidative stress. Oxidative stress is closely related to various diseases, including cancer. There are many evidences that ROS are pivotal in cancer progression (via damage of DNA leading to genomic instability) and regression (via cell death induction through oxidative stress burst). Antioxidants stabilize free radicals and, in turn, prevent the oxidative stress, playing a key role in protection of the body, In this context, natural plants-derived antioxidants are universally considered very important for the prevention and treatment of oxidative stress and cancer. However, a dual role of plants in ROS generation or scavenging is recognized as plants extracts can also increase ROS production in the cells. Consequently, the role of plant extracts in ROS balancing inside cancer cells is a very fascinating feature in phytotherapy.

Among the plants reported in traditional medicine as a very panacea in active compounds, Carica papaya and Azadiracta indica (also known as Neem) extracts from different parts (leaves, seeds, fruits, etc.) are scientifically validated in the treatment of several diseases, including cancer. In this context, the two plants have different impact on cancer cell lines. In particular hydro-alcoolic extract of Neem leaves shows a pro-oxidant activity in hepatoma HepG2 cells, whereas water extract of C. papaya seeds exerts an anti-oxidant activity in leukemia HL-60 cells. Neem extract is unable to quench oxidative stress induced on HepG2 and synergizes with hydrogen peroxide (H2O2) in inducing cell death. Conversely, C. papaya extract quenches ROS induced by H2O2 in HL-60 cells but at the same time negatively affects cell viability.

These evidences corroborate the idea that the extracts from plants could act in patients with cancer to modulate oxidative homeostasis and obtain benefit during cancer therapy.

Vital Probes 2. Cell Viability and Signaling

In this chapter several fluorescent probes for the assessment of cell viability, types of cell death, identification of signals, cellular traffic and connections will be described. These biomedical fields have increasing interest [1-3]. The fluorescence histochemistry of enzymatic activity is currently applied in assays for cell viability, apoptotic processes, and detection of reactive oxygen species (ROS). Several probes of viability and signaling are also markers of oxidative stress and redox visualization. Numerous probes are now commercially available for studies on cell metabolism and toxicity, signal transduction, drug screening, molecular diagnosis, etc. Fluorescent labels and biosensors are applied to perform quali- and quantitative analysis of normal and pathological cell processes (i.e. sensing dyes for trans-membrane potential, ions, ROS, pH, etc). There exist also approaches to the direct real-time signal imaging of live-cells in vitro and in vivo, and for 2D and 3D analysis.

Bioactive Compounds and Prostate Cancer Therapy

Prostate cancer (PCa) is the most common solid neoplasm and is one of the major causes of cancer mortality among men. Recent studies have shown the beneficial effect of some nutrients in PCa management. Natural phytochemicals often have pleiotropic effects, targeting virtually every molecular signaling pathway, which makes them promising agents for multi-target anti-cancer therapy. Furthermore, they are usually well-tolerated, easily available and cost-efficient. This chapter describes the variety of naturally occurring bioactive compounds used for the treatment and prevention of prostate cancer, especially focusing on dietary polyphenols and their analogs, including green tea polyphenols, resveratrol and curcuminoids, vitamins, organosulfur compounds from onions and garlic (predominantly allyl derivatives) and phytochemicals from cruciferous vegetables. While some of these compounds (e.g. curcumin and sulforaphane) have established anticarcinogenic properties, the others provide contradictory results in preclinical and clinical studies. Selenium and vitamin E supplementation is the most prominent case of such controversy. In this chapter, we cover molecular mechanisms that lead to PCa progression, as well as key mechanisms of antitumor action. Impact of different nutrients on cancer-associated epigenetic modifications is analyzed. Results of epidemiological studies and dietary interventions conducted to date are also provided. Main challenges associated with design and interpretation of such interventions are discussed, together with major issues of developing naturally occurring compounds into clinically used agents. While a promising scientific area, further research is required to completely elucidate the relationship between nutrients and PCa.