Osthole (7-methoxy-8-isoamyl alkenyl coumarin) has been reported to exhibit marked anticancer effects on several types of cancer. The expression levels of matrix metalloproteinase-9 (MMP-9) are closely associated with the pathogenesis of glioma. Furthermore, it is reported that the upregulation of microRNA‑16 (miR‑16) by the MMP‑9 signaling pathway can restrain the proliferation of cancer cells. To examine whether osthole increases the anticancer effect on human glioma cells in the present study, the common glioma cell line, U87, was treated with osthole at concentrations of 0, 50, 100 and 200 µΜ. The effects of osthole on cell viability were determined using a 3‑(4,5‑dimethylthiazol‑2‑thiazolyl)‑2,5‑diphenyl‑tetrazolium bromide assay. The rate of cellular apoptosis was analyzed by measuring the activity of caspase‑3 and using flow cytometry. The expression of MMP‑9 was determined using gelatin zymography assays and the expression of miR‑16 was determined using reverse transcription‑quantitative polymerase chain reaction. The results demonstrated that osthole significantly suppressed the proliferation and accelerated the apoptosis of the U87 cells. Furthermore, increased expression levels of miR‑16 and reduced protein expression levels of MMP‑9 were found in the U87 cells. In addition, miR‑16 was found to regulate the expression of MMP‑9 in the U87 cells through transfection of miR‑16 precursor and anti‑miR‑16 into the U87 cells. In conclusion, these observations indicated that osthole suppressed the proliferation and accelerated the apoptosis of human glioma cells through upregulation of the expression of miR‑16 and downregulation of the expression of MMP-9.
An intramolecular formal [3 + 2] cationic cycloaddition between benzylic carbocation and styrene was developed for the total synthesis of codonopiloneolignanin A. Further study shows benzocycloheptene as a good substrate for 1,3-dipolar cycloaddition, and a model study toward cephalocyclidine A skeleton was reported.
Cochlearol B and Ganocins A-C are polycyclic meroterpenoids isolated from Ganoderma cochlear with renoprotective effect and as AChE inhibitor, respectively. Using a strained cyclobutane as overbred intermediate, a unified synthesis of the four natural products is reported, including a scalable eight-step synthesis of cochlearol B. The synthesis of cochle-arol B features a [2+2] photocycloaddition to forge a highly substituted cyclobutane, and the first-generation synthesis of ganocin A features a complex carbocation rearrangement sequence initiated by an epoxide-opening. Moreover, a bio-inspired unprecedent oxidative cleavage of cyclobutane ring enables the second-generation synthesis of ganocin A ac-complished concisely in 10 steps. Furthermore, ganocins B and C were obtained after decarboxylation and a one pot re-action of -elimination, dehydration and deprotection. Our synthesis adds insight to the plausible non-enzymatic biogen-esis of these natural products.
The present study aimed to evaluate the inhibitory effects of an irinotecan derivative, ZBH‑1208, on brain tumors, and to explore the underlying molecular mechanisms. To determine the effects of ZBH‑1208, a brain tumor mouse model was established by transplanting B22 cells. Subsequently, the visceral indices of immune organs and white blood cell counts were determined, and the effects of ZBH‑1208 on the expression levels of cell cycle‑related proteins were assessed by western blotting. The tumor inhibition rates of 20 and 40 mg/kg ZBH‑1208 were 11.7 and 54.1%, respectively. Compared with the negative control group, ZBH‑1208 barely affected visceral indices or white blood cell count. Furthermore, the expression levels of p53, p21, cyclin‑dependent kinase 7 (CDK7), Wee1, phosphorylated (p)‑cell division cycle 2 (CDC2) (Tyr15), p‑CDC2 (Thr161) and cyclin B1 proteins were upregulated, whereas the expression levels of cyclin E were downregulated, and those of CDC2, CDK2 and CDC25C were barely altered. In conclusion, the present study demonstrated that ZBH‑1208 suppressed the growth of B22 mouse brain tumor xenografts, but did not affect their visceral indices or white blood cell counts. It was suggested that ZBH‑1208 exerted its effects by regulating the expression of p53, p21, Wee1, p‑CDC2 (Tyr15) and cyclin E proteins.
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