Kathiresan Suresh

Anti-tumor initiating potential of andrographolide in 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis.

The aim of the study was to investigate the chemopreventive potential of andrographolide in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch of golden Syrian hamsters at a 100% incidence on painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Marked abnormalities in the status of detoxification enzymes, lipid perxodiation and antioxidants were noticed in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/ kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also restored the status of the above mentioned biomarkers. The present study thus demonstrates the chemopreventive potential of andrographolide in DMBA-induced hamster buccal pouch carcinogenesis, which is probably due to its antioxidant potential as well as modulating effect on xenobiotic metabolising enzymes during DMBA-induced oral carcinogenesis.

Chemopreventive and antioxidant efficacy of (6)-paradol in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis

The present study evaluated the chemopreventive potential of (6)-paradol, a pungent phenolic constituent of ginger, on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. The mechanistic pathway for the chemopreventive potential of (6)-paradol was evaluated by measuring the status of tumor incidence, volume and burden as well as by analyzing the status of phase II detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinoma was induced in hamster buccal pouches by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% tumor formation with marked biochemical abnormalities in tumor-bearing animals compared to control animals. Oral administration of 30 mg/kg b.w. (6)-paradol to DMBA-treated hamsters on alternate days from DMBA painting for 14 weeks, significantly reduced the formation of tumors and improved the status of detoxification agents, lipid peroxidation and antioxidants. Therefore, the present study suggests that (6)-paradol has potent chemopreventive, anti-lipid peroxidative and antioxidant potentials as well as a modulating effect on phase II detoxification enzyme and reduced glutathione (GSH) in DMBA-induced hamster buccal pouch carcinogenesis.

Altered pattern of lipids in plasma and erythrocyte membranes of rheumatoid arthritis patients.

The present study has investigated the levels of lipids, lipoprotein cholesterol (HDL and LDL cholesterol), thiobarbituric acid reactive substances (TBARS) and vitamin E in plasma and erythrocyte membranes of twenty two clinically diagnosed adult rheumatoid arthritis patients and an equal number of age matched healthy subjects. The levels of lipids and lipoprotein cholesterol were markedly reduced in patients with rheumatoid arthritis as compared to healthy subjects. The altered lipid pattern may be related to decreased lipoprotein cholesterol, fatty acids and impairment in antioxidant defence mechanism.

Anti-cell Proliferative and Anti-angiogenic Potential of Andrographolide During 7,12- Dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

[6]-Shogaol attenuates inflammation, cell proliferation via modulate NF-κB and AP-1 oncogenic signaling in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis

Nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) is a major transcription factor which regulates many biological and pathological processes such as inflammation and cell proliferation, which are major implicates in cancer progression. [6]-Shogaol ([6]-SHO) is a major constituent of ginger, exhibits various biological properties such as anti-oxidants, anti-inflammation and anti-tumor. Recently, we proven that [6]-SHO prevents oral squamous cell carcinoma by activating proapoptotic factors in in vitro and in vivo experimental model. However, the preventive efficacy of [6]-SHO in 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis (HBP) has not been fully elucidated, so far. Hence, we aimed to investigate the effect of [6]-SHO on inflammation and cell proliferation by inhibiting the translocation of NF-κB and AP-1 in DMBA induced HBP carcinogenesis. In this study, we observed upregulation of inflammatory markers (COX-2, iNOS, TNF-α, interleukin-1 and -6), cell proliferative markers (Cyclin D1, PCNA and Ki-67) and aberrant activation of NF-κB, AP-1, IKKβ, c-jun, c-fos and decreased IκB-α in DMBA induced hamsters. Conversely, oral administration of [6]-SHO strongly inhibited constitutive phosphorylation and degradation of IκB and inhibit phosphorylation of c-jun, c-fos, resulting in inhibition of nuclear translocation of NF-κBp65 and AP-1. Thus, inhibition of NF-κB and AP-1 activation by [6]-SHO attenuates inflammation and cell proliferative response in DMBA induced hamsters. Our finding suggested that [6]-SHO is a novel functional agent capable of preventing DMBA induced inflammation and cell proliferation associated tumorigenesis by modulating multiple signalling molecules.

Diosmin induce apoptosis through modulation of STAT-3 signaling in 7,12 dimethylbenz(a)anthracene induced harmster buccal pouch carcinogenesis

Diosmin is naturally found flavanoid in many citrus fruits known to have anti-inflammatory, antihyperglycemic, antioxidant and antimutagenic properties. Effects of Diosmin on IL-6/STAT-3 expression in hamster buccal pouch carcinogenesis remain unclear. Alterations in many genes encode crucial proteins, which regulate cell proliferation, differentiation and apoptosis have been implicated in oral cancer. In the present study, we investigated the effect of dietary Diosmin on IL-6/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by examining the protein expression of IL-6/STAT-3 and its related genes. Immunoblotting and immunohistochemical analyses revealed that Diosmin (100mg/kgb.w) supplement inhibits key events in signaling especially STAT-3 phosphorylation and subsequent nuclear translocation. Results revealed that inhibition of proliferation and angiogenesis is associated with regulation of the STAT-3 pathway; where Diosmin prevents phosphorylation of JAK-1 which was ascend by IL-6, thereby inhibiting STAT-3 phosphorylation. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade in favor of apoptosis. Transmission electron microscopic studies proved the effect of Diosmin on ultrastructural changes. Finally our results provide significant evidence that Diosmin prevents the development and progression of HBP carcinomas through the inhibition of IL-6/STAT-3 signaling and its downstream events. Thus, Diosmin functions as a potent inhibitor of tumor development and progression by targeting IL-6/STAT-3 signaling may be an ideal candidate for cancer chemoprevention.

Modulating effect of Hypnea musciformis (red seaweed) on lipid peroxidation, antioxidants and biotransforming enzymes in 7,12-dimethylbenz (a) anthracene induced mammary carcinogenesis in experimental animals

Background: Breast cancer is the second most widespread diagnosed cancer and second leading cause of cancer death in women. Objective: The present work was carried out to evaluate the chemo preventive potential of Hypnea musciformis (ethanol extract) seaweed on oxidative stress markers, bio transforming enzymes, incidence of tumors, and pathological observation in 7,12-dimethylbenzanthracene (DMBA) exposed experimental mammary carcinogenesis. Materials and Methods: Female Sprague–Dawley rats were randomly divided into four groups. Rats in the group 1 served as control. Rats in the group 2 and 3 received a single subcutaneous injection of DMBA (25 mg/kg body weight (b.w)) in the mammary gland to develop mammary carcinoma. In addition, group 3 rats were orally administrated with 200 mg/kg between of H. musciformis along with DMBA injection and group 4 rats received ethanolic extract of H. musciformis every day orally (200 mg/kg b.w) throughout the experimental period of 16 weeks. Results: Our results revealed that treatment with H. musciformis ethanolic extract to DMBA treated rats significantly reduced the incidence of tumor and tumor volume as compared to DMBA alone treated rats. Moreover, our results showed imbalance in the activities/levels of lipid peroxidation by products, antioxidant enzymes, and bio transforming phase I and II enzymes in the circulation, liver and mammary tissues of DMBA treated rats which were significantly modulated to near normal on treatment with ethanolic extract of H. musciformis. All these alterations were supported by histochemical findings. Conclusion: The results obtained from this study suggest that chemo preventive potential of H. musciformis ethanol extract is probably due to their free radicals quenching effect and modulating potential of bio transforming enzymes during DMBA exposed experimental mammary carcinogenesis.