Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells

Abstract

It is often postulated that trans-3,4',5-trihydroxystilbene (resveratrol, RES) exhibits cell growth regulatory and chemopreventive activities. However, mechanisms by which this polyphenol inhibits tumor cell growth, and its therapeutic potential are poorly understood. Using various human leukemia cells, we have first defined the anti-tumoral doses of this compound. RES inhibited the proliferation and induced the apoptosis of all tested lymphoid and myeloid leukemia cells with IC 50 ⍧ 5-43 µM. Prior to apoptosis, RES-induced caspase activity in a dose-dependent manner and cell cycle arrest in G 2 /M-phase, correlating with a significant accumulation of cyclins A and B. Leukemia cell death with RES required both caspase-dependent and -independent proteases, as it was significantly inhibited by simultaneous addition of Z-VAD-FMK and leupeptin to these cultures. While RES did not affect non-activated normal lymphocytes, this agent decreased the growth and induced the apoptosis of cycling normal human peripheral blood lymphocytes at lower concentrations (IC 50 <8 µM) than those required for most leukemia cells. RES also induced the apoptosis of early normal human CD34 ⍣ cells and decreased the number of colonies generated by these precursor cells in a dose-dependent manner (IC 50 ⍧ 60 µM). Together, the data point to the complexity of RESmediated signaling pathways and revealed the high antiproliferative and proapoptotic activities of RES in normal cycling hemopoietic cells.

In Vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs

“…However, we found the cytotoxicity of TSO in the RAW 264.7 macrophages to be notably less than that of the hydroxylated stilbenes. Although the present study did not determine the type of death incurred by macrophages treated by PIC, RES, or TPS, previous reports have shown that these stilbenes, in particular, can kill other types of cells by apoptosis [14,17,20]. Currently, our lab is exploring the exact mechanism through which the macrophages are dying and this subject will be communicated in a future manuscript relating to this topic.…”

“…In addition to their antioxidant properties, it is worthy to note that cytotoxic effects of RES, PIC, and TPS have also been reported. In this regard, RES has demonstrated pro-oxidant, genitourinary, immunotoxic, hepatotoxic and genotoxic properties [18][19][20][21][22][23]. PIC, a metabolite of RES, has been reported to induce apoptosis of transformed and primary lymphocytes [17] and to also exhibit cytotoxic actions towards macrophages in vitro [24].…”

Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer

“…In addition, resveratrol-treated cells were shown to have a low level of cdk7 kinase-Thr (161)-phosphorylated cdk1 [168]. In vitro and in vivo studies show that resveratrolinduced cell cycle arrest in G2/M phase is associated with an accumulation of cyclins A and B [157,164,169,170] …”

Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest

“…7,8 It is very well known that resveratrol shows antioxidant, cardioprotective, chemopreventive, anticarcinogenic, antiproliferative and anti-inflammatory effects both in vivo and in vitro. 9,10 Resveratrol has been shown to induce apoptosis in a variety of cancers such as chronic myeloid leukemia (CML), acute myeloid leukemia (AML), breast, prostate, colon and lung cancers. [11][12][13] The exact mechanism of resveratrol mediated anticancer effect is not fully identified.…”