Vanadium as a chemoprotectant: effect of vanadium(III)-L-cysteine complex against cyclophosphamide-induced hepatotoxicity and genotoxicity in Swiss albino mice.

Vanadium is an essential micronutrient for living systems and has antioxidant and genoprotective property. In the present study, the protective role of an organovanadium compound vanadium(III)-L-cysteine (VC-III) was evaluated against hepatotoxicity and genotoxicity induced by cyclophosphamide (CP) (25 mg/kg b.w., i.p.) in Swiss albino mice. Treatment with VC-III (1 mg/kg b.w., p.o.) mitigated CP-induced hepatic injury as indicated by reduction in activities of alanine transaminase, aspartate transaminase, alkaline phosphatase by 1.57-, 1.58- and 1.32-fold in concomitant treatment schedule and by 1.83-, 1.77- and 1.45-fold in pretreatment schedule, respectively, and confirmed by histopathological evidences. Parallel to these changes, VC-III ameliorated CP-induced oxidative stress in liver by 1.46-, 1.26-, 1.32- and 1.42-fold in concomitant treatment group and by 1.95-, 1.40-, 1.46- and 1.73-fold in pretreatment group at the level of H2O2, superoxide, nitric oxide and lipid peroxidation, respectively. VC-III also enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione (reduced) level in mice liver by 1.46-, 1.37-, 1.29-, 1.44- and 1.45-fold in concomitant treatment schedule and by 1.64-, 1.65-, 1.42-, 1.49- and 1.57-fold in pretreatment schedule, respectively. In addition, the organovanadium compound could efficiently attenuate CP-induced chromosomal aberrations, DNA fragmentation and apoptosis in bone marrow cells and DNA damage in lymphocytes by 1.49-, 1.43-, 1.48- and 1.59-fold in concomitant treatment group and by 1.76-, 1.92-, 1.99- and 2.15-fold in pretreatment group, respectively. Thus, the present study showed that VC-III could exert protection against CP-induced hepatotoxicity and genotoxicity.

Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways.

The role of dietary factors in inhibiting or delaying the development of non-melanoma skin cancer (NMSC) has been investigated for many years. Cardamom, which is a dietary phytoproduct, has been commonly used in cuisines for flavour and has numerous health benefits, such as improving digestion and stimulating metabolism and having antitumorigenic effects. We have investigated the efficacy of dietary cardamom against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomatogenesis in Swiss albino mice that closely resembles human NMSC. Mice were grouped into normal wild type (untreated), vehicle-treated (acetone), carcinogen-treated (DMBA), and DMBA and cardamom-treated (DMBA+CARD) to delineate the role of cardamom against DMBA-induced papillomatogenesis. Oral administration of cardamom to DMBA-treated mice up-regulated the phase II detoxification enzymes, such as glutathione-S-transferase and glutathione peroxidase, probably via activation of nuclear factor erythroid-2-related factor 2 transcription factor in 'DMBA+CARD' mice. Furthermore, reduced glutathione, glutathione reductase, superoxide dismutase and catalase were also up-regulated by cardamom in the same 'DMBA+CARD' group of mice compared with DMBA-treated mice. Cardamom ingestion in DMBA-treated mice blocked NF-κB activation and down-regulated cyclo-oxygenase-2 expression. As a consequence, both the size and the number of skin papillomas generated on the skin due to the DMBA treatment were reduced in the 'DMBA+CARD' group. Thus, the results from the present study suggest that cardamom has a potential to become a pivotal chemopreventive agent to prevent papillomagenesis on the skin.

Effect of garlic on lipid peroxidation and antioxidation enzymes in DMBA-induced skin carcinoma.

OBJECTIVE: Naturally occurring phytochemicals display an active cancer preventive strategy to inhibit, delay, or reverse human carcinogenesis. Studies have indicated that certain daily-consumed dietary phytochemicals have cancer protective effects mediated by carcinogens. Lipid peroxide plays a detrimental role in all cancers including skin carcinogenesis. Garlic, a phytochemical, has acquired a special position in the folklore of many cultures as a formidable prophylactic and therapeutic medicinal agent. In this report, we pursue the chemopreventive effect of aqueous garlic on skin carcinogenesis. METHODS: "Swiss albino mice" were divided into five groups depending on the combination of skin cancer-inducing 7,12-dimethylbenz[a]anthracene and garlic treatments. Histology of the affected skin and biochemical assays for lipid peroxide, catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase were performed to demonstrate the effect of garlic in mice. Immunoblotting was performed with cyclo-oxygenase-2, p53, and caspase-3 to demonstrate expressions of the respective proteins in skin lysates. RESULTS: Garlic extracts inhibited the oxidative modification of lipids, thus protecting cells from injury by the oxidized molecules. The best chemopreventive action of garlic was observed in mice in which garlic treatment was performed before and after the induction of skin carcinogenesis. Garlic ingestion delayed formation of skin papillomas in animals and simultaneously decreased the size and number of papillomas, which was also reflected in the skin histology of the mice treated. CONCLUSION: The protective effects against skin cancer elicited by garlic in mice are believed to be due at least in part to the induction cellular defense systems.

Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice.

One of the most promising strategies for cancer prevention today is chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices. Among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin papillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted with croton oil were investigated. Significant reduction in papilloma formation was found with saffron application in the pre-initiation and post-initiation periods, and particular when the agent was given both pre- and post-initiation. The inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide dismutase (SOD).

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.

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.

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, gamma-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, NF-kappaB 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.

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 cell's 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.