Shwu-Bin Lin

Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest

The medicinal mushroom Ganoderma lucidum (G. lucidum) has been used in the Orient for the prevention and treatment of various diseases including cancer. Except for the immune enhancing properties of its polysaccharide constituent, very little is known about the anticancer activity of another major constituent, triterpenes. In this report, we studied the anticancer mechanism of triterpene-enriched extracts from G. lucidum. The triterpene-enriched fraction, WEES-G6, was prepared from mycelia of G. lucidum by sequential hot water extraction, removal of ethanol-insoluble polysaccharides and then gel-filtration chromatography. We found that WEES-G6 inhibited growth of human hepatoma Huh-7 cells, but not Chang liver cells, a normal human liver cell line. Treatment with WEES-G6 caused a rapid decrease in the activity of cell growth regulative protein, PKC, and the activation of JNK and p38 MAP kinases. The changes in these molecules resulted in a prolonged G2 cell cycle phase and strong growth inhibition. None of these effects were seen in the normal liver cells. Our findings suggest that the triterpenes contained in G. lucidum are potential anticancer agents.

Arachidin-1, a peanut stilbenoid, induces programmed cell death in human leukemia HL-60 cells.

The stilbenoids, arachidin-1 (Ara-1), arachidin-3, isopentadienylresveratrol, and resveratrol, have been isolated from germinating peanut kernels and characterized as antioxidant and anti-inflammatory agents. Resveratrol possesses anticancer activity, and studies have indicated that it induces programmed cell death (PCD) in human leukemia HL-60 cells. In this study, the anticancer activity of these stilbenoids was determined in HL-60 cells. Ara-1 had the highest efficacy in inducing PCD in HL-60 cells, with an approximately 4-fold lower EC50 than resveratrol. Ara-1 treatment caused mitochondrial membrane damage, activation of caspases, and nuclear translocation of apoptosis-inducing factor, resulting in chromosome degradation and cell death. Therefore, Ara-1 induces PCD in HL-60 cells through caspase-dependent and caspase-independent pathways. Ara-1 demonstrates its efficacy as an anticancer agent by inducing caspase-independent cell death, which is an alternative death pathway of cancer cells with mutations in key apoptotic genes. These findings indicate the merits of screening other peanut stilbenoids for anticancer activity.

Photochemical cleavage of single- and double-stranded oligonucleotides by 3-(p-tolylamino)-1,5-azulenequinone

Irradiation, with 350 nm UV light, of specially designed and synthesized single- and double-stranded oligodeoxyribonucleotides in the presence of 3-(p-tolylamino)-1,5-azulenequinone produced fragments resulting from the cleavage at the deoxyguanosine residue only. The cleaving efficiency was greater for a single strand than a double helix. The efficiency was increased for a less stable double helix, or while the deoxyguanosine residue therein was located at a bulge, at a hairpin loop, or towards the end of the helix.

Interaction Between 3-(p-Tolylamino)-1,5-azulenequinone and the Deoxyguanosine Residue in Various Oligonucleotides upon Photolysis¶

Abstract Eight single-stranded oligodeoxyribonucleotides 32P-labeled at the 5′-end were synthesized; they were annealed with the complementary oligodeoxyribonucleotides to form the corresponding double-stranded helices. These duplexes possessed standard Watson–Crick base pairs, locally perturbed sites of a base mismatch, or a bulge. Further, 5′–32P-labeled oligodeoxyribonucleotides with a hairpin loop were also synthesized. Cleavage of these single- and double-stranded oligodeoxyribonucleotides selectively at the deoxyguanosine residue was accomplished by use of 3-(p-tolylamino)-1,5-azulenequinone 1 upon irradiation with 350 nm UV light. The single strands were cleaved more efficiently than the double-helices. For the helices containing a deoxyguanosine residue at a bulge, at a hairpin loop or toward the end, the cleaving efficiency was increased. Computation results indicate that two possibilities exist for agent 1 to form two “Watson–Crick type” hydrogen bonds with guanine in single-stranded oligodeoxyribonucleotides; yet, only one possibility exists in duplexes.