A comprehensive review on RNA interference-mediated targeting of interleukins and its potential therapeutic implications in colon cancer.

Colon cancer is the world's fourth leading cause of death. It is cancer of the latter part of the large intestine, i.e. the colon. Chronic inflammation over a long period also leads to the development of cancer. Cancer in the colon region is arduous to diagnose and is detected at a later stage when it metastasizes to other parts of the body like the liver, lungs, peritoneum, etc. Colon cancer is a great example of solid tumours associated with chronic inflammation. Although conventional therapies are effective, they lose their effectiveness beyond a certain point. Relapse of the disease occurs frequently. RNA interference (RNAi) is emerging as a great tool to specifically attack the cancer cells of a target site like the colon. RNAi deals with epigenetic changes made in the defective cells which ultimately leads to their death without harming the healthy cells. In this review, two types of epigenetic modulators have been considered, namely siRNA and miRNA, and their effect on interleukins. Interleukins, a class of cytokines, are major inflammatory responses of the body that are released by immune cells like leukocytes and macrophages. Some of these interleukins are pro-inflammatory, thereby promoting inflammation which eventually causes cancer. RNAi can prevent colon cancer by inhibiting pro-inflammatory interleukins.

Anti-proliferative and apoptotic properties of a peptide from the seeds of Polyalthia longifolia against human cancer cell lines.

The peptides produced enzymatically from various plants have shown various biological activities including cytotoxicity. Different types of cytotoxic peptides have been reported from the seeds and leaves of Violaceae, Rubiaceae and Annonaceae families. In this study, we report purification and characterization of peptide(s) showing cytotoxic activity against A549 and HeLa cancer cell lines from the seeds of Polyalthia longifolia (Annonaceae). Seed proteins of P. longifolia were extracted and hydrolyzed using trypsin. The enzyme hydrolysate was applied on to a Sephadex G10 column and eluted using Tris-HC1 buffer (pH 7.5). Two fractions F1 and F2 were obtained, of which F2 showed significant cytotoxic activity against lung (A549) cancer cells at 10 microg/mL and cervical (HeLa) cancer cell lines at 30 microg/mL, as revealed by the MTT assay. DNA fragmentation was observed in the tested cancer cell lines treated with F2 peptide at a concentration of 10microg/mL and 30 pg/mL, respectively. Further, increased number of apoptotic cells was observed in sub-G0 phase of cell cycle of A549 and HeLa cell lines, when treated with 10 microg/mL and 30 microg/mL of F2, as revealed by the flow cytometric analyses. FTIR spectrum of F2 peptide detected the presence of stretching vibrations of carboxylic acid OH residue with peak at 3420 cm-and carbonyl (C=O) groups at 1636 cm-1, respectively. RP-HPLC analysis of F2 peptide showed a single peak at a retention time of 12.8 min detected at 280 nm, depicting the purity of F2 to be more than 90%. LC-ESI-MS/MS analysis showed the average theoretical mass of F2 to be 679.8 using m/z ratios. In conclusion, the findings suggest that F2 peptide is an effective inducer of apoptosis of cancer cells, thus offers an important strategy in the development of cancer therapeutics.

Induction of apoptotic effects of antiproliferative protein from the seeds of Borreria hispida on lung cancer (A549) and cervical cancer (HeLa) cell lines.

A 35 KDa protein referred to as F3 was purified from the seeds of Borreria hispida by precipitation with 80% ammonium sulphate and gel filtration on Sephadex G-100 column. RP-HPLC analysis of protein fraction (F3) on an analytical C-18 column produced a single peak, detected at 220 nm. F3 showed an apparent molecular weight of 35 KDa by SDS PAGE and MALDI-TOF-MS analyses. Peptide mass fingerprinting analysis of F3 showed the closest homology with the sequence of 1-aminocyclopropane-1-carboxylate deaminase of Pyrococcus horikoshii. The protein (F3) exhibited significant cytotoxic activity against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner at concentrations ranging from 10 µg to 1000 µg/mL, as revealed by the MTT assay. Cell cycle analysis revealed the increased growth of sub-G0 population in both cell lines exposed to a concentration of 1000 µg/mL of protein fraction F3 as examined from flow cytometry. This is the first report of a protein from the seeds of Borreria hispida with antiproliferative and apoptotic activity in lung (A549) and cervical (HeLa) cancer cells.