Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells

Abstract

Jaspamide (asplakinolide) is a natural peptide isolated from marine sponges of Jaspis species and has fungicidal and growth-inhibiting activities. We characterized the jasplakinolide-induced loss of viability by programmed cell death in the HL-60 human promyelocytic leukemia cell line and found that this process was accompanied by neutral endopeptidase (NEP)/CD10 expression on the surface of the apoptotic cells. HL-60 cells do not normally express detectable amounts of NEP/CD10 on their surface or intracytoplasmically, but upon jaspamide treatment, CD10 was synthesized de novo, its expression being inhibited by cycloheximide pretreatment. Once synthesized, NEP/CD10 interfered with the jasplakinolide signal delivered to HL-60 cells. Inhibition of NEP/CD10 by the NEP inhibitor phosphoramidon or by an anti-CD10 monoclonal antibody significantly increased apoptosis induction. The appearance of CD10 on the cell surface was blocked by preincubation of the cells with the monocytic/macrophage-differentiating agents vitamin D3 and phorbol 12-myristate 13-acetate, but not by the granulocytic differentiating agents retinoic acid or dimethyl sulfoxide. Moreover, in the promonocytic U937 and mature monocytic THP-1 cell lines, jaspamide induced apoptosis but not CD10 expression. In HL-60 cells, CD10 expression was partially but not totally blocked by the broad-spectrum caspase inhibitor benzyloxacarbonyl-Val-Ala-Asp-fluoromethylketone, indicating a connection between apoptosis induction and CD10 synthesis. Our findings suggest that the CD10 expression is related to the programmed cell death induction by jaspamide, and also with the process of granulocytic differentiation in HL-60 cells.

Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion

“…27 Still others have demonstrated that JP acts by inducing apoptosis through a caspase 3 dependent pathway. 31 Despite these hypothetical difficulties, our results support the claim that JP acts as a cytoskeleton stabilizer at the dose tested here (Figure 1), since all JP treated groups showed reversion of cytoskeletal disruption. This reversal was also observed in the groups in which disruption had previously been provoked by Swinholide, demonstrating Jasplakinolide's ability to counteract the effect of a disruptor of this kind.…”

Comparative Study of Two Helix Aspersa Extracts on Tumor Cell Lines (Hut-78 and Seax) Proliferation and MMP-9 Secretion

“…One of these peptides was tested on tumor lines. Research teams had found that this compound induces apoptosis in these tumor lines by activating caspase-3 and decreasing the expression of bcl-2 [26,28]. This same compound had anti mitotic effect by binding to tubulin (microtubules protein, a major component of the cytoskeleton) [29,30].…”

Targeting Cellular Proapoptotic Agents from Marine Sources

“…Further study reveals that cephalostatin 1 also inactivates the Bcl-2 via hyperphosphorylation by JNK [104]. Like cephalostatin 1, Jaspamide induces apoptosis by activation of caspase-3 and decrease of Bcl-2 protein levels, but it also involves increased Bax level via a caspase-independent pathway as an additional mechanism [105]. Another small compounds bromophenol derived from algae, bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces mitochondrial apoptosis in K562 cells via activation of caspases and changes the Bcl-2/Bax in vitro [106].…”