5-fluorouracil increases the chemopreventive potentials of resveratrol through DNA damage and MAPK signaling pathway in human colorectal cancer cells.

Resveratrol (Res) can modulate multiple cellular pathways relevant for tumorigenesis but is less effective in colon cancer compared to breast cancer. To increase the chemopreventive potential of Res in combination with 5-fluorouracil (5-FU), a systematic study was carried out in colon cancer cells. HCT-116 cells were treated with Res and 5-FU and several cell-based assays, such as MTT, clonogenic, wound healing, DAPI, comet assay, and Western blot, were performed. A significant inhibition of cell proliferation, migration, and increased apoptosis were observed when moderate concentration of Res (15 microM) was associated with very low concentration of 5-FU (0.5 microM). This combination caused apoptosis by blocking the cells at S phase and enhanced the DNA damage. Expression levels of p-JNK and p-p38 were increased without affecting pERK. 5-FU could be used as a therapeutic modality to improve efficacy of Res-based chemotherapy against colon cancer.

Structural elaboration of a natural product: identification of 3,3'-diindolylmethane aminophosphonate and urea derivatives as potent anticancer agents.

An approach involving rational structural elaboration of the biologically active natural product diindolylmethane (DIM) with the incorporation of aminophosphonate and urea moieties toward the discovery of potent anticancer agents was considered. A four-step approach for the synthesis of DIM aminophosphonate and urea derivatives was established. These novel compounds showed potent anticancer activities in two representative kidney and colon cancer cell lines, low toxicity to normal cells, higher potency than the parent natural product DIM and etoposide, and potent inhibition of cancer cell migration. Biophysical and immunological studies, including DAPI nuclear staining, western blot analysis with apoptotic protein markers, flow cytometry, immunocytochemistry, and comet assays of the two most potent compounds revealed good efficacies in apoptosis and DNA damage. It was found that down-regulation of nuclear factor κB (NF-κB p65) could be an important mode of action in apoptosis, and the two most potent derivatives were found to be more potent than parent compound DIM in the down-regulation of NF-κB. Our results show the importance of structural elaboration of DIM by rational incorporation of aminophosphonate and urea moieties to produce potent anticancer agents; they also suggest that this approach using other structurally simple bioactive natural products as scaffolds holds promise for future drug discovery and development.

Breast cancer scenario in a regional cancer centre in Eastern India over eight years--still a major public health problem.

In spite of screening and early diagnostic tests, the upward trend of breast cancer has become a matter of great concern in both developed and developing countries. The data collected by Population Based Cancer Registry in Chittaranjan National Cancer Institute, a regional cancer centre in Kolkata, from 1997 to 2004 gives an insight about the scenario of breast cancer in this part of Eastern India. The total no of female breast cancer cases were steadily increasing from 1997 to 2001 and only slightly lower from 2002 to 2004. and majority were in the 40-49 year old age group during this period. The next most commonly affected age group was 50-59 years. Regarding the distribution according to treatment, the main modality was surgery and radiotherapy followed by combined surgery, chemotherapy and radiotherapy and then combined surgery and chemotherapy. The commonest type was ductal followed by lobular cancer. In this eight year study in CNCI, status of patients on last day of the respective year was assessed. Number of patients alive was 43.5% in 1997. The percentage gradually increased up to 2000 and then gradually decreased to 47.4% in 2004. Also with every passing year, percentage mortality gradually decreased from 25.7% in 1997 to 16.8% in 2004. Better pattern of care (diagnosis and treatment) was reflected in this picture. However, lost to follow up, which also implies non compliance to treatment, increased to 30.8% in 1997 to 35.8% in 2004. Due to the small number of male breast cancers, only female cases were considered. In conclusion, breast cancer continues to be a major problem in Kolkata, India.

Childhood cancer burden in part of eastern India--Population Based Cancer Registry data for Kolkata (1997-2004).

The increasing magnitude of childhood cancer has become a threatening problem in developing countries like India. Data from the Population Based Cancer Registry (PBCR) of Chittaranjan National Cancer Institute (CNCI), Kolkata during 1997 to 2004 were here analyzed. CNCI receives patients from West Bengal as well as other neighboring states and countries. Childhood cancer was found to account for 2.21% of all cancers registered in this period. Crude and age adjusted rates were higher among boys than girls, with leukemia as the commonest (36.8%) followed by lymphomas (14.8%) and soft tissue tumors (8.0%). Chemotherapy was the major modality of treatment given, followed by radiotherapy and surgery. The study provides useful information on the prevalence and management protocols of childhood cancer in this part of eastern India.