Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells (original) (raw)
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The FEBS Journal, 2020
L‐leucyl‐leucine methyl ester (LLOMe) is a lysosomotropic detergent, which was evaluated in clinical trials in graft‐vs‐host disease because it very efficiently killed monocytic cell lines. It was also shown to efficiently trigger apoptosis in cancer cells, suggesting that the drug might have potential in anticancer therapy. Using U‐937 and THP‐1 promonocytes as models for monocytic cells, U‐87‐MG and HeLa cells as models for cancer cells, and noncancerous HEK293 cells, we show that the drug triggers rapid cathepsin C‐dependent lysosomal membrane permeabilization, followed by the release of other cysteine cathepsins into the cytosol and subsequent apoptosis. However, monocytes were found to be far more sensitive to the drug than the cancer and noncancer cells, which is most likely a consequence of the much higher intracellular levels of cathepsin C—the most upstream molecule in the pathway—in monocytic cell lines as compared to cancer cells. Overexpression of cathepsin C in HEK293 c...
Anticancer research
Previous studies indicate that Cathepsin L (CatL) is involved in brain tumour progression. Here, CatL in tumour cell invasion and apoptosis has been studied. Human glioblastoma cell line U87 was transfected with CatL cDNA in sense and antisense orientations. The in vitro invasiveness was tested in modified Boyden chambers. Apoptosis was determined by fluorescent staining, caspase activity, and by Bax and Bcl-2 mRNA levels. Surprisingly, the invasiveness of U87 cells was not impaired by genetic down-regulation of CatL expression. In the CatL antisense clones, the apoptotic rate induced by either intrinsic or extrinsic stimuli was increased, whereas CatL sense transfection seemed to protect the cells from apoptosis. Increased chemoresistance of tumour cells may be associated with increased levels of CatL and may have potential application in gene therapy, which would augment the apoptosis of glioblastoma cells induced by chemotherapy.
Purpose: B cell chronic lymphocytic leukemia (B-CLL) is an neoplastic disorder characterized by alterations in the pathways of programmed cell death (apoptosis). Deregulation of apoptosis pathways also contributes to chemoresis-tance of B-CLL cells. Therefore, it is not surprising that induction and acceleration of apoptosis represent key point in novel B-CLL therapeutic protocols. The present study was designed to investigate the effects of two natural products, Immunarc forte and Korbazol on the in vitro survival of leu-kemic cells. Methods: Peripheral blood mononuclear cells (PBMC) from 20 B-CLL patients and 20 healthy donors were used for cytotoxicity studies. Cytotoxic activity of the tested products were assessed by the MTT colorimetric assay and the type of cell death was determined by flow cytometry. Results: We found that Korbazol was selectively cyto-toxic against B-CLL cells, but the cytotoxic activity of Im-munarc forte was much weaker. Of note, synergy was shown between these two drugs, and this effect was also selective, without affecting the normal mononuclear cells. According to Annexin-V binding, Korbazol and Immunarc forte induced apoptotic type of cell death in B-CLL cells. Moreover, treatment with Korbazol, but not with Immunarc forte, decreased spontaneous apoptosis in cultured normal polymorphonu-clear cells. Conclusion: Our findings imply that Korbazol is as potential therapeutic agent that induces apoptosis of B-CLL cells. The resistance of normal mononuclear cells and anti-apoptotic effects on normal polymorphonuclear cells, as well as its ability to synergize with Immunarc forte, warrants further investigation and supports their therapeutic application in the treatment of B-CLL.