Cytotoxic and apoptotic activities of novel Pd(II) complexes against human leukemia cell lines in vitro

In the investigation for alternative chemotherapeutic strategies against leukemia, Pd(II) complexes were synthesized and investigated for cytotoxic and apoptotic properties on two human leukemia cell lines (HL-60 and K562). Pd(II) complexes (Pd-5a and Pd-6a) with 5a and 6a as ligands were synthesized and characterized by ¹H-NMR and F-TIR. The cytotoxicity of the compounds was quantified using MTT method. Bax, Bcl-2, and caspase 3 gene expression levels were estimated using RT-qPCR. Here we show that Pd(II) complexes have important cytotoxic activity on human leukemia cell lines. RT-qPCR indicated that Bax and caspase 3 gene expression levels were increased after 24 h treatment with Pd-5a and Pd-6a complexes in both HL-60 and K562 cells at some selected dose. Furthermore, Bcl-2 gene expression level decreased after 24 h treatment with Pd-5a and Pd-6a complexes in K562 cells at all selected dose. In HL-60 cells, only one selected Pd-5a dose (25 µM) decreased the gene expression level of Bcl-2. The results obtained in the present investigation indicate that these two newly synthesized Pd(II) complexes have apoptotic effects at appropriate doses through caspase 3 and Bax genes and might represent a novel potentially active agents for the management of human leukemia cell lines.     

Effect of purified fractions from cell culture supernate of high‐density pre‐B acute lymphoblastic leukemia cells (ALL3) on the growth of ALL3 cells at low density

The mechanisms underlying the aberrant growth and interactions between cells are not understood very well. The pre‐B acute lymphoblastic leukemia cells directly obtained from an adult patient grow very poorly or do not grow at all at low density (LD), but grow better at high starting cell density (HD). We found that the LD ALL3 cells can be stimulated to grow in the presence of diffusible, soluble factors secreted by ALL3 cells themselves growing at high starting cell density. We then developed a biochemical purification procedure that allowed us to purify the factor(s) with stimulatory activity and analyzed them by nanoliquid chromatography‐tandem mass spectrometry (nanoLC‐MS/MS). Using nanoLC‐MS/MS we have identified several proteins which were further processed using various bioinformatics tools. This resulted in eight protein candidates which might be responsible for the growth activity on non‐growing LD ALL3 cells and their involvement in the stimulatory activity are discussed.     

Stereoselective synthesis of (6S) and (6R)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one and their cytotoxic activity against cancer cell lines

Stereoselective total synthesis of α,β-unsaturated lactone (1a), isolated from Ravensara crassifolia, has been achieved efficiently starting from chiral 2,3-O-isopropylidene-d-glyceraldehyde (3) followed by asymmetric allylation and ring-closing metathesis. The antiproliferative activities of compounds 1a, 1b and the unusual bicyclic compound 2 were evaluated against three-cancer cell lines, THP-1 and U-937 (leukemia) and A-375 (melanoma).     

Separation and identification of steroidal compounds with cytotoxic activity against human gastric cancer cell lines <Emphasis Type="Italic">in vitro</Emphasis> from the rhizomes of <Emphasis Type="Italic">Paris polyphylla</Emphasis> var. <Emphasis Type="Italic">chinensis</Emphasis>

A novel steroidal saponin, along with 12 known steroidal compounds, was isolated from the rhizomes of Paris polyphylla var. chinensis. Spectral data, including two-dimensional NMR, showed that the structure of the novel saponin was 3β,21-dihydroxypregnane-5-en-20S-(22,16)-lactone-1-O-α-L-rhamnopyranosyl(1→2)-[β-D-xylopyranosyl(1→3)]-β-D-glucopyranoside. The isolated steroidal compounds were evaluated for their cytotoxic activity on human gastric cancer cell line HepG₂, SGC7901, BxPC3. Diosgenin-3-O-α-L-rhamnopyranosyl(1→2)[α-L-rabinofuranosyl(1→4)]-β-D-glucopyranoside exhibited the most potent cytotoxic activity among the isolated steroids. Published in Khimiya Prirodnykh Soedinenii, No. 6, pp. 556–560, November–December, 2007.