Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines.

The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER(+) and ER(-) breast cancer cell lines.

Results of urinary dissolution therapy for radiolucent calculi.

PURPOSE: In this paper we present our experience with dissolution therapy of radiolucent calculi. MATERIALS AND METHODS: This was a retrospective analysis of patients who were offered urinary dissolution therapy between January 2010 and June 2011. Patients were treated with tablets containing potassium citrate and magnesium oxide. Partial dissolution was defined as at least a 50% reduction in stone size. Patients with complete or partial dissolution were classified in the successful dissolution group. Patients with no change, inadequate reduction, increase in stone size and those unable to tolerate alkali therapy were classified as failures. Patient sex, stenting before alkalinization, stone size, urine pH at presentation and serum uric acid levels were analyzed using Fisher t-test for an association with successful dissolution. RESULTS: Out of 67, 48 patients reported for follow up. 10 (15%) had complete dissolution and 13 (19%) had partial dissolution. Alkalinization was unsuccessful in achieving dissolution in 25 (37%). Stenting before alkalinization, patient weight (< 60 vs. > 75kg) and serum uric acid levels (≤ 6 vs. > 6) were the only factors to significantly affected dissolution rates (p = 0.039, p 0.035, p 0.01 respectively). CONCLUSIONS: A policy of offering dissolution therapy to patients with radiolucent calculi had a successful outcome in 34% of patients.

Attenuation of non-enzymatic thermal glycation of bovine serum albumin (BSA) using ß-carotene.

Although heat treatment of proteins is believed to promote and accelerate glycation, the accompanying structural changes in proteins because of heat denaturation and/or glycation are not completely understood. In addition, there is an increasing interest for inhibitors of thermal glycation in food processing. ß-Carotene is a naturally occurring carotenoid found in many vegetables, fruits and herbs, with known antioxidant activity. However, it has not been identified if ß-carotene possesses anti-glycation activity. We have tested the anti-glycation capacity of ß-carotene in the bovine serum albumin (BSA)/glucose system that was heated to 55 and 65 °C for 3 days and studied the level of glycation, conformational alterations in BSA, and changes in hydrophobicity, due to thermal treatment and/or glycation. ß-Carotene exhibited significant inhibitory effects on the formation of advanced glycation end products (AGEs) and also prevented the secondary structural changes in BSA due to thermal glycation. Our results represent the anti-glycative properties of ß-carotene in food systems where such thermal conditions prevail.