Ila Das

Redox Regulation in Cancer: A Double-edged Sword with Therapeutic Potential

Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS) and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV) exposures, γ-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NFκB and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis.

Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study

Cancer chemoprevention is the use of natural, synthetic or biological substances to reverse or prevent the development of cancer. Saffron is a naturally derived plant product that acts as an antispasmodic, diaphoretic, carminative, emmenagogic and sedative. Our aim in this study was to investigate the chemopreventive effect of aqueous saffron on chemically induced skin carcinogenesis using a histopathological approach. Mice were divided into five groups: carcinogen control (CC), normal control (NC) and saffron-treated Groups A, B and C. Groups A, B, C and CC mice received three topical applications of 7,12 dimethylbenz[a]anthracene (DMBA) followed by croton oil on shaven dorsal skin for 8 weeks. NC mice received topical skin applications of the vehicle, acetone, only. Saffron infusion was fed orally to three groups of mice either before (Group A) or after (Group C) or both before and after (Group B) DMBA applications. The activities of antioxidant enzymes glutathione-S transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in liver tissue samples taken at 0, 6, 10 and 12 weeks from all groups were assessed. Standard histological examination of skin demonstrated a beneficial action of saffron in mice where saffron treatments were given both before and after the induction of skin carcinogenesis. Saffron ingestion inhibited the formation of skin papillomas in animals and simultaneously reduced their size. In conclusion, saffron inhibits DMBA-induced skin carcinoma in mice when treated early. This may be due, at least in part, to the induction of cellular defense systems.

Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.

Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and cells own antioxidant defenses that in part lead to numerous carcinogenesis. Several phytochemicals, derived from vegetables, fruits, herbs and spices, have demonstrated excellent chemopreventive properties against carcinogenesis by regulating the redox status of the cells during oxidative stress. I3C (indole-3-carbinol) and DIM (diindolylmethane) are the phytochemicals that are found in all types of cruciferous vegetables and demonstrated exceptional anti-cancer effects against hormone responsive cancers like breast, prostate and ovarian cancers. Novel analogs of I3C were designed to enhance the overall efficacy, particularly with respect to the therapeutic activity and oral bioavailability and that results in several patent applications on symptoms associated with endometriosis, vaginal neoplasia, cervical dysplasia and mastalgia. Likewise, DIM and its derivatives are patented for treatment and prevention of leiomyomas, HPV infection, respiratory syncytial virus, angiogenesis, atherosclerosis and anti-proliferative actions. On the other hand, phytochemicals in cardamom have not been explored in great details but limonene and cineole demonstrate promising effects against carcinogenesis. Thus studies with selected phytochemicals of cardamom and bioavailability research might lead to many patent applications. This review is focused on the patents generated on the effects of I3C, DIM and selected phytochemicals of cardamom on carcinogenesis.

Association of Breast Cancer with Sleep Pattern - A Pilot Case Control Study in a Regional Cancer Centre in South Asia

The rising trend of breast cancer both in developed and developing countries is a real threat challenging all efforts to screening, prevention and treatment aspects to reduce its impact. In spite of modern preventive strategies, the upward trend of breast cancer has become a matter of great concern in both developed and developing countries. Chittaranjan National Cancer Institute is a premier regional cancer institute in eastern region of India catering to a large number of cancer patients every year. A pilot case control study of fifty breast cancer patients and 100 matched controls was conducted during 2013 to evaluate the effects of habitual factors like working in night shift, not having adequate sleep, and not sleeping in total darkness on breast cancer of women. The study revealed that not sleeping in total darkness was associated with higher odds of outcome of breast cancer of women. This positive correlation can play a vital role in formulation of preventive strategies through life style modification.

Protective effect of garlic in skin cancer

The incidence of cancer is rising in almost all parts of the world because of changes in the environment, changes in life style and food habits as well as due to growing industrialization and modernization. UV exposures from the sun in the exposed areas of the body are the prime locations of developing skin cancer. The rate of skin cancer is rising in an alarming rate and more than 10 million cases of skin cancer patients register each year for treatments. Epidemiological evidences demonstrate that naturally occurring phytochemicals are highly capable of inhibiting or delay the progression of several human carcinogenesis. Garlic and its major organosulfur components have acquired a special position in the medicinal history due to its anti-viral, anti-bacterial and fungicidal properties. Cancer chemoprevention using garlic as a dietary phytochemical is an active area of research and here we discuss the potential role of garlic and its components to inhibit, delay or reverse skin carcinogenesis. Both oral and topical application of various forms of garlic showed protection against chemical carcinogen induced skin papillomagenesis in mice. The protection occurs best when garlic was used in the diet prior to induction of skin papillomas by the carcinogens. Garlic inhibits the deleterious action of the carcinogens by downregulating lipid peroxides and at the same time upregulates several antioxidants, antioxidation enzymes and phase II detoxification enzymes. Garlic also downregulates COX-2, which is a marker of carcinogenesis progression. Garlic exerts its chemopreventive activities by modulating p53 and PI3K/Akt signaling pathways as well as promotes ROS generation and apoptosis in the skin papilloma cells. Inclusion of garlic in regular diet will eliminate several physical abnormalities and will promote healthy lifestyle.

Abstract 2880: Spices suppress oxidative stress during DMBA induced skin carcinogenesis in mice, mimicking human non-melanoma skin cancer

Background: Cancer chemoprevention is the use of natural, synthetic or biologic substances to reverse, suppress, or prevent the development of cancer. Spices like cinnamon, cardamom and cumin are the naturally occurring phytoproducts that display an active cancer preventive strategy to inhibit, delay or reverse the human carcinogenesis. Aims and Objectives: Our aim of this study is to decipher the chemopreventive effect of aqueous infusion of the spices as a diet on DMBA induced skin carcinogenesis, which mimics UV radiation mediated non melanoma skin cancer that has high mortality rate if not diagnosed early. Research Design and Methodology: Female Swiss Albino Mice have been divided into 5 groups in each case. Normal control (NC) and DMBA treated control (CC) mice received acetone and DMBA/croton oil on it9s dorsally shaven skin for eight weeks, respectively. Aqueous suspensions of the spices were orally administered to three groups of mice either before or after or both before and after DMBA applications on the shaved skin during the entire study period. Treated skins were excised after harvesting the mice and H & E staining, immunohistochemistry assays for lipid peroxides, antioxidation enzymes activities, immunoblotting, cell proliferation and apoptosis were performed. Results: All the spices demonstrate inhibition of the skin papillomagenesis. The best chemopreventive actions of these spices were observed when the spice treatments were performed both before and after the induction of skin carcinogenesis by DMBA. An up-regulation of the phase II detoxification enzymes and induction of non-protein thiol antioxidants were observed in mice treated with the spices. Additionally, cumin and cardamom demonstrate downregulation of COX-2 expression, inhibit cell proliferation and block p53-induced apoptosis. Cardamom stimulates NRF2 and inhibits NF-κB transcription factors to demonstrate its beneficial action against skin carcinogenesis. Conclusion: Spices inhibit DMBA induced skin carcinoma in mice when treated early and it is believed to be due, at least in part, to the induction of cellular defense systems. We are in a process of identifying unique chemical components of these spices to maximize the benefits. References: 1. Das, I., and Saha, T.; Nutrition. (2009); 25(4):459-471. 2. Das, I., Das, S. and Saha, T.; Acta Histochem. (2009); (In Press) 3. Das, I., Rana, T., Sengupta, A., and Saha, T.; J. Biol. Chem. 2009; (In Revision) 4. Acharya, A, Das, I., Chandhok, D., and Saha, T.; Oxidative Stress and Cellular Longevity; 2009; (In Press) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2880.