2 research outputs found
Transforming Growth Factor Beta-Induced Protein (Big-H3) C-Terminal Fragment Peptide EPSIM Triggers Apoptosis in Human Osteosarcoma Cells
No full textThe author has granted permission for their work to be available to the general public.Transforming growth factor beta induced gene human clone 3 (BIG-H3), is an extracellular matrix protein whose expression is upregulated on treatment with TGF-beta 1. BIG-H3 protein regulates several physiological processes including cell adhesion and migration. Structural analysis of BIG-H3 revealed a secretory signal protein at the N-terminus followed by four FAS I domains and two distinct integrin binding motifs near the C-terminus: RGD and EPDIM. The C-terminal portion of the peptide is known to undergo proteolytic cleavage that provides several fragments. As various studies implicated that RGD sequence triggered apoptosis in CHO and HeLa cells, it was important to establish which proteolytic fragment triggers apoptosis in human osteosarcoma cells (Skonier et.al.,2009). A previous study conducted by this laboratory demonstrated that, truncated C-terminal fragment is necessary to induce apoptosis and when the C-terminal portion is blocked apoptosis induced by BIG-H3 is low (Zamilpa et.al.,2009). The current study investigated that when compared, EPDIM peptide with varying concentrations can induce apoptosis at a higher percentage than RGD in human osteosarcoma cells.Integrative Biolog
Photo-Induced Cytotoxicity and Anti-Metastatic Activity of Ruthenium(II)-Polypyridyl Complexes Functionalized with Tyrosine or Tryptophan
No full textThe synergistic effect of oxygen, light, and photosensitizer (PS) has found applications in medicine for the treatment of cancer through photodynamic therapy (PDT). Induction of apoptosis to cancerous cells will prevent tumor metastasis that spreads cancer cells to the neighboring organs/tissues. Herein, we report the two apoptotic Ru(II)–polypyridyl complexes that are functionalized with pendant amino acid moieties tyrosine (1) and tryptophan (2), respectively. These two water soluble complexes were found to interact strongly (K1a = (1.18 ± 0.28) × 105 M−1 and K2a = (1.57 ± 0.77) × 105 M−1) with CT-DNA. Isothermal titration calorimetry (ITC) studies revealed that these complexes bind to CT-DNA through an entropically driven process. Both the complexes showed photo-induced cytotoxicity and exhibit apoptotic activity under photo-irradiation conditions. The comet assay indicated that these complexes can damage cellular DNA, which is attributed to the significant build-up of 1O2 level even on irradiation with low intensity light (10 J cm−2, λRange 450–480 nm). This photoinduced DNA damage and apoptosis in A549 cells was induced by reactive oxygen species (ROS) and occurred through up-regulation of apoptotic marker caspase-3. Control experiments under dark conditions revealed an insignificant cytotoxicity towards these cells for two photosensitive molecules
