Harmine, a β-carboline alkaloid isolated from the seeds of Peganum harmala, possesses both antitumor and anti‑nociceptive effects and inhibits human DNA topoisomerase. However, no detailed data are available concerning the mechanisms of harmine in human colorectal carcinoma SW620 cells. In the present study, we demonstrated that harmine inhibited the proliferation of SW620 cells in a dose-dependent manner using MTT and clone formation assays, and the IC50 value of harmine on the growth inhibition of SW620 cells for 48 h was 5.13 µg/ml. PI staining showed that harmine altered the cell cycle distribution by decreasing the proportion of cells in the G0-G1 phase and increasing the proportion in the S and G2-M phase. The expression level of cyclin D1 was decreased, while the expression of cyclin A, E2 and B1, CDK1/cdc2, Myt-1 and p-cdc2 (Tyr15) were increased, which was in accordance with the S and G2/M phase arrest. Hoechst 33258 staining revealed nuclear fragmentation, chromosomal condensation and cell shrinkage in the SW620 cells treated with harmine. Flow cytometry revealed that the percentage of apoptotic sub-G1 cells increased from 7.19 to 26.58%, while in the control group, sub-G1 cells only increased from 1.53 to 1.60%. Furthermore, early and late apoptotic cells were increased from 11.96 to 26.38% when incubated with the indicated concentration of harmine for 48 h, while in the control group, <8% of cells underwent apoptosis. JC-1 staining revealed that harmine decreased mitochondrial transmembrane potential (ΔΨm). The apoptosis of SW620 cells was also detected by western blot analysis, showing caspase-3 and -9, and PARP activation; the downregulation of Bcl-2, Mcl-1, Bcl-xL; and the upregulation of Bax. The expression of p-ERK, p-Akt (Ser473) and p-Akt (Thr308) was inhibited, and phosphorylation of downstream targets of Akt, such as p-FoxO3a and p-GSK‑3β were also attenuated. In conclusion, harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways.

Norcantharidin, a low-toxic analog of the active anticancer compound cantharidin in Mylabris, can inhibit proliferation and induce apoptosis of multiple types of cancer cells. However, the anticancer activities of norcantharidin with respect to neuroblastoma, and its underlying mechanisms, have not been investigated. Therefore, our study was designed to determine the efficacy of norcantharidin on SK-N-SH neuroblastoma cell death and to elucidate detailed mechanisms of activity. In the present study, norcantharidin suppressed the proliferation and cloning ability of SK-N-SH cells in a dose-dependent manner, apparently by reducing the mitochondrial membrane potential and arresting SK-N-SH cells at the G2/M stage, accompanied by elevated expressions of p21 and decreased expressions of cyclin B1 and cell division control 2. Treatment by norcantharidin induced significant mitophagy and autophagy, as demonstrated by a decrease in Translocase Of Outer Mitochondrial Membrane 20 (TOM20), increased beclin1 and LC3-II protein expression, reduced protein SQSTM1/p62 expression, and accumulation of punctate LC3 in the cytoplasm of SK-N-SH cells. In addition, norcantharidin induced apoptosis through regulating the expression of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 and B-cell lymphoma 2-associated X protein/myeloid cell leukemia 1 and activating caspase-3 and caspase-9-dependent endogenous mitochondrial pathways. We also observed an increase in phosphor-AMP-activated protein kinase accompanied with a decrease in phosphor-protein kinase B and mammalian target of rapamycin expression after treatment with norcantharidin. Subsequent studies indicated that norcantharidin participates in cellular autophagy and apoptosis via activation of the c-Jun NH2-terminal kinases/c-Jun pathway. In conclusion, our results demonstrate that norcantharidin can reduce the mitochondrial membrane potential, induce mitophagy, and subsequently arouse cellular autophagy and apoptosis; the AMP-activated protein kinase, protein kinase B/mammalian target of rapamycin, and c-Jun NH2-terminal kinases/c-Jun signaling pathways are widely involved in these processes. Thus, the traditional Chinese medicine norcantharidin could be a novel therapeutic strategy for treating neuroblastoma.

Cu2þ -doped ZnS quantum dots were synthesized by a chemical precipitation method in water/ethanol solution. The quantum dots obtained were characterized by X-ray diffraction, transmission electron microscopy and spectroscopy techniques including X-ray photoelectron spectroscopy. ] ¼ 1:1. For powders, only the green emission is the main luminescence centre, and the integrated intensity in the blue emission region of sample 1 is stronger than that of sample 2. Compared with the spectrum of CuS powders, the X-ray-induced Auger electron spectrum of Cu L 3 M 45 M 45 in ZnS quantum dots shows a unique spectral characteristic. The 3d level of the Cu 2þ ion is split into two different energy levels at 334.0 and 347.2 eV, respectively.

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