Apoptosis of Human Burkitt’s lymphoma cells induced by 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077)

Abstract

Piperazine is one of the heterocycles which are associated with diverse pharmacological activities. 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077) is a trisubstituted piperazine which contains a trimethoxybenzene ring and a benzhydrylpiperazine fragment, both of which can induce cell proliferation regression by different mechanisms. We have therefore examined the effects of PMS-1077 on Human Burkitt's lymphoma cells (Raji). The viability of Raji cells was determined by MTT assay and also assessed by trypan blue dye exclusion method. The results demonstrate that PMS-1077 can suppress the proliferation of Raji cells in a dose- and timedependent manner, while inhibit colony formation ability of Raji cells merely in a dose-dependent manner in vitro. Meanwhile, morphological changes were observed using fluorescence microscope. Flow cytometric analysis through PI stains showed that PMS-1077 blocked the growth of Raji cells in the G(0)/G(1) period, and induced apoptosis of Raji cells after 48 h of incubation. Cell apoptosis induced by PMS-1077 was further confirmed by staining with Annexin-V FITC and PI. Preliminary study by molecular docking suggests that PMS-1077 may inhibit tubulin polymerization. More experiments are in progress in our laboratory to reveal the mode of action of PMS-1077 in the induction of apoptosis of Raji cells.

Dracorhodin perchlorate suppresses proliferation and induces apoptosis in human prostate cancer cell line PC-3

“…To observe the morphological changes in apoptotic cells, the AO and EB staining was performed [10] . Briefly, cells were harvested with 0.125% trypsin and 0.01% EDTA, re-suspended in 95 μL of RPMI-1640 medium, and incubated with 5 μL of AO/EB staining solution (100 mg/L PBS with each dye) at room temperature for 15 min.…”

PMS1077 Sensitizes TNF-α Induced Apoptosis in Human Prostate Cancer Cells by Blocking NF-κB Signaling Pathway

“…While further improving these properties and taking into account the flexibility of these compounds, we were also engaged to study the potential effects of these compounds in other pathological conditions, such as inflammation and tumor genesis. Our previous work demonstrated that PMS1077 could induce apoptosis of Raji cells, but the mechanism of action remains unclear [5].…”

Synthesis and cytotoxicity studies of novel benzhydrylpiperazine carboxamide and thioamide derivatives

“…As shown in Table 2, all tested compounds were screened with mean 50% growth inhibition concentration (GI 50 ) in micromolar concentration range.…”

“…It can be noted that thioamides show higher activity than their carboxamide derivatives, which can be exemplified by compounds 5j (GI 50 The most active compounds against MCF-7 cell line are 5u (GI 50 ¼ 6.14 mM) and 6e (GI 50 ¼ 4.94 mM). Furthermore, we observed that compound 6e was less toxic in MCF-12A (GI 50 ¼ 8.5 mM), which is a normal-like breast epithelial cell line (Table 4).…”

“…Anticancer activity of benzhydrylpiperazines has recently advanced [44][45][46][47][48][49][50][51] . Kumar et al have performed cytotoxicity assays to several 1-benzhydrylpiperazine derivatives substituted with variable sulfonyl chlorides, acid chlorides and isothiocyanates.…”