Sarmistha Banerjee

Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo(a)pyrene-induced lung carcinogenesis.

One of the most promising strategies for cancer prevention is chemoprevention by daily used food and beverages. Black tea, the most widely consumed beverage, is a source of compounds with antioxidative, antimicrobial, antimutagenic and anticarcinogenic properties. Lung cancer is the most common cause of cancer deaths in both men and women worldwide. Over one million people around the world are likely to be killed by lung cancer due to increased tobacco smoking and environmental pollutants, especially car exhausts. Therefore chemopreventive intervention using black tea and its active components may be a viable means to reduce lung cancer death. In the present investigation, we used benzo(a)pyrene (BP) to induce lung carcinogenesis in mice for the assessment of potential apoptosis-inducing and proliferation-suppressing effects of theaflavins and epigallocatechin gallate, active components of black tea. Hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks respectively, were effectively reduced after treatment with theaflavins and epigallocatechin gallate. Significant reduction in number of proliferating cells and increased number of apoptotic cells was also found on the 8th, 17th and 26th week of treatment with theaflavins and epigallocatechin gallate in BP-exposed mice. Our observation suggests a promising role for black tea polyphenols in the prevention of lung cancer.

Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: Downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway

BACKGROUND Eugenol is the active component of essential oil isolated from clove (Syzigium aromaticum). Eugenol has antimutagenic, antigenotoxic, anti-inflammatory properties. The anticarcinogenic effect of eugenol was evident in different types of cell lines. However, its anticarcinogenic effect in in vivo has not yet been fully explored. OBJECTIVE The aim of this study is to evaluate the chemopreventive potential of eugenol in an experimental skin carcinogenesis mice model system. METHOD Skin tumor was induced by topical application of DMBA croton oil in Swiss mice. To assess the chemopreventive potential of eugenol, it was orally administered 15 days prior carcinogen treatment. The development of skin carcinogenesis was confirmed by histopathological analysis. Cellular proliferation and apoptosis in the skin tumor were analyzed by in situ cellular proliferation and in situ cell death assay. Expression of some proliferation and apoptosis associated genes was analyzed by RT-PCR and protein expression was analyzed by Western blot. RESULTS Reduction in incidence and sizes of skin tumors along with overall increase in survival of mice were seen due to eugenol treatment. Restriction of skin carcinogenesis at the dysplastic stage along with reduced rate of cellular proliferation and increase in apoptosis were evident in eugenol treated skin tumors. Eugenol treatment led to the downregulation of c-Myc, H-ras and Bcl2 expression along with upregulation of P53, Bax and active Caspase-3 expression in the skin lesions. CONCLUSION Restriction of skin carcinogenesis at dysplastic stage by eugenol was due to attenuation of c-Myc, H-ras and modification of some p53 associated gene expression.

Epigallocatechin gallate induced apoptosis in Sarcoma180 cells in vivo: Mediated by p53 pathway and inhibition in U1B, U4-U6 UsnRNAs expression

The aim of this study was to understand the mode of action of tea polyphenol epigallocatechin gallate (EGCG) in vivo. Swiss albino mice were treated i.p. with EGCG at two different doses i.e. 12-mg/kg body weight and 15-mg/kg body weight, for 7 days prior to inoculation of Sarcoma180 (S180) cells and continued for another 7 days. The growth of the S180, harvested 7 days after inoculation, was significantly reduced due to treatment with EGCG. The flowcytometric analysis of S180 cells, showed significant increase in apoptosis and reduction in the number of cells in G2/M phase of cell cycle due to treatment with EGCG. The induction of apoptosis has also been confirmed by the TUNEL and DNA fragmentation assays. Both RT-PCR and Western blot analysis showed significant up-regulation of p53 and bax, and down-regulation of bcl-2 and c-myc due to EGCG treatment. No changes in the expression pattern of p21, p27, bcl-xl, mdm2 and cyclin D1 were seen. Interestingly, there was significant down-regulation of spliceosomal uridylic acid rich small nuclear RNAs (UsnRNAs) U1B and U4-U6 due to EGCG treatment. This indicates that these UsnRNAs may be involved in the apoptosis process. Taken together, our study suggests that in vivo EGCG could induce apoptosis in S180 cells through alteration in G2/M phase of the cell cycle by up-regulation of p53, bax and down-regulation of c-myc, bcl-2 and U1B, U4-U6 UsnRNAs.

Differential alterations in metabolic pattern of the spliceosomal UsnRNAs during pre-malignant lung lesions induced by benzo(a)pyrene : Modulation by tea polyphenols

The differential alterations of the spliceosomal UsnRNAs (U1, U2, U4, U5, and U6) were reported to be associated with cellular proliferation and development. The attempt was made in this study to analyze the metabolic pattern of the spliceosomal UsnRNAs during the development of pre-malignant lung lesions induced in experimental mice model system by benzo(a)pyrene (BP) and also to see how tea polyphenols, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), modulate the metabolism of these UsnRNAs during the lung carcinogenesis. No significant changes in the level of the UsnRNAs were seen in the inflammatory lung lesions at 9th week due to treatment of BP. However, there was significant increase in the level of U1 (∼2.5 fold) and U5 (∼47%) in the hyperplastic lung lesions at 17th week. But in the mild dysplastic lung lesions at 26th week, the level of UsnRNAs did not change significantly. Whereas, in the dysplastic lung lesions at 36th week there was significant increase in the level of the U2 (∼2 fold), U4 (∼2.5 fold) and U5 (∼2 fold). Due to the EGCG and ECG treatment the lung lesions at 9th week appeared normal and in the 17th, 26th, and 36th week it appeared as hyperplasia. The level of the UsnRNAs was significantly low in the lung lesions at 9th week (only U2 and U4 by EGCG), at 17th week (only U1 by EGCG/ECG), at 26th week (U1 by ECG; U2, U4 and U5 by EGCG/ECG) and at 36th week (U1 by ECG, U2 and U4 by EGCG/ECG). Whereas, there was significant increase in the level of U5 (by EGCG/ECG) and U6 (by EGCG only) in the lung lesions at 36th and 26th week respectively. This indicates that the metabolism of the spliceosomal UsnRNAs differentially altered during the development of pre-malignant lung lesions by BP as well as during the modulation of the lung lesions by the tea polyphenols.

Growth hormone: a newly identified developmental organizer

The sexually dimorphic expression of cytochromes P450 (CYP) drug-metabolizing enzymes has been reported in all species examined. These sex differences are only expressed during adulthood and are solely regulated by sex differences in circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoform profiles are permanent and immutable, suggesting that adult CYP expression requires imprinting. As the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats, whereas others received concurrent physiologic replacement of rat GH. The results demonstrate that adult male GH activation of the signal transduction pathway regulating expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting, without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. As there are other adult metabolic functions also regulated by GH, pediatric drug therapy known to disrupt GH secretion could unintentionally impair adult health.