Evaluation of the cytotoxic and genotoxic effects of goniothalamin in leukemic cell lines

Abstract

The cytotoxic and genotoxic effects of goniothalamin, a plant styryllactone, were evaluated using the 3-(4,5 -dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the Alkaline Comet assay respectively in human leukemic cell lines. Following 72 h of treatment, the IC 50 values of goniothalamin in human HL-60 promyelocytic leukemia cells and CEM-SS T-lymphoblastic cells were 4.5 µg/mL and 2.4 µg/mL respectively. The genotoxicity of goniothalamin in both HL-60 and CEM-SS cells was detected as early as 2 h following treatment at IC 10 and IC 25 concentrations. However, pretreatment with the antioxidant N-acetyl-cysteine (NAC) at 1 mM for 30 minutes did not abrogate genotoxicity of this compound. This result suggests that primary induction of DNA damage by goniothalamin may not involve oxidative damage. In conclusion, our results demonstrate genotoxic damage induced by goniothalamin in leukemic cells. Further studies are needed to ascertain the mode of action of goniothalamin in inducing DNA damage.

Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells

“…S-GNT, in turn, was genotoxic only for the tumor cell line MCF-7. These results are consistent with previous reports that attribute the cytotoxic effect of goniothalamin to its genotoxicity (Inayat-Hussain et al, 2009;Kuo et al, 2011;Rajab et al, 2005). In addition, the gene GADD45a, which is regulated in response to DNA damage, was upregulated after R-GNT exposure.…”

“…Among all of the bioactive properties of goniothalamin that have been described, one of the most notable is its anti-proliferative activity against various tumor cell lines, including breast cancer (Alabsi et al, 2012;Chen et al, 2005;de Fatima et al, 2005;Wattanapiromsakul et al, 2005), liver cancer (Al-Qubaisi et al, 2011;Tian et al, 2006), leukemic cells (Inayat-Hussain et al, 1999;Inayat-Hussain et al, 2009;Petsophonsakul et al, 2013;Rajab et al, 2005), colon cancer (Alabsi et al, 2012;de Fatima et al, 2005;Wattanapiromsakul et al, 2005), lung cancer (de Fatima et al, 2005;Semprebon et al, 2014;Wattanapiromsakul et al, 2005), kidney cancer (de Fatima et al, 2008;Wattanapiromsakul et al, 2005), ovarian and prostate cancer (de Fatima et al, 2005). Furthermore, the synthetic enantiomer, (S)goniothalamin, also exhibits antiproliferative potential (de Fatima et al, 2008;Fatima et al, 2006;Semprebon et al, 2014), but its mechanism of action remains poorly understood.…”

Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with Goniothalamin Extracted from Goniothalamus macrophyllus

“…Goniothalamin had been able to induce cytotoxicity in a variety of cancer cell lines including gastric , kidney (768-0), breast carcinomas (MCF-7, T47D and MDA-MB-231) and leukemia (HL-60, Jurkat and CEM-SS) (Chen et al, 2005;Rajab et al, 2005;InayatHussain et al, 2010). Goniothalamin has been proved to be only cytotoxic to ovarian cancer cell line (Caov-3) without causing cell death in normal kidney cell (MDBK) as happened in tamoxifen or taxol treated cells (Lin and Pihie, 2003).…”

Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines

“…it is a novel compound with putative anti-cancer properties (Lin and Pihie, 2003;Chen et al, 2005;Al-Qubaisi et al, 2011). Goniothalamin extracted from Goniothalamus andersonii had been able to induce cytotoxicity in a variety of cancer cell lines including cervical (HeLa), gastric (HGC-27), kidney (768-0), breast carcinomas and leukemia (HL-60, Jurkat and CEM-SS) (Rajab et al, 2005;Inayat-Hussain et al, 2010). Goniothalamin has been proved to be only cytotoxic to ovarian cancer cell line (Caov-3) without causing cell death in normal kidney cell (MDBK) as happened in tamoxifen or taxol treated cells (Lin and Pihie, 2003).…”