Selective Cytotoxicity of Goniothalamin against Hepatoblastoma HepG2 Cells

Abstract

Liver cancer has become one of the major types of cancer with high mortality and liver cancer is not responsive to the current cytotoxic agents used in chemotherapy. The purpose of this study was to examine the in vitro cytotoxicity of goniothalamin on human hepatoblastoma HepG2 cells and normal liver Chang cells. The cytotoxicity of goniothalamin against HepG2 and liver Chang cell was tested using MTT cell viability assay, LDH leakage assay, cell cycle flow cytometry PI analysis, BrdU proliferation ELISA assay and trypan blue dye exclusion assay. Goniothalamin selectively inhibited HepG2 cells [IC50 = 4.6 (±0.23) µM in the MTT assay; IC50 = 5.20 (±0.01) µM for LDH assay at 72 hours], with less sensitivity in Chang cells [IC50 = 35.0 (±0.09) µM for MTT assay; IC50 = 32.5 (±0.04) µM for LDH assay at 72 hours]. In the trypan blue dye exclusion assay, the Viability Indexes were 52 ± 1.73% for HepG2 cells and 62 ± 4.36% for Chang cells at IC50 after 72 hours. Cytotoxicity of goniothalamin was related to inhibition of DNA synthesis, as revealed by the reduction of BrdU incorporation. At 72 hours, the lowest concentration of goniothalamin (2.3 µL) retained 97.6% of normal liver Chang cells proliferation while it reduced HepG2 cell proliferation to 19.8% as compared to control. Besides, goniothalamin caused accumulation of hypodiploid apoptosis and different degree of G2/M arrested as shown in cell cycle analysis by flow cytometry. Goniothalamin selectively killed liver cancer cell through suppression of proliferation and induction of apoptosis. These results suggest that goniothalamin shows potential cytotoxicity against hepatoblastoma HepG2 cells.

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

“…These results conducted to other studies investigated the cytotoxic effect of Goniothalamin towards human breast cancer, vascular smooth muscle cells (VSMCs), Jurkat leukemia cells, HL-60 leukemia cells, Chinese hamster ovary (CHO) and hepatoblastoma HepG2 cells (Ali et al, 1997;Pihie et al, 1998;Inayat-Hussain et al, 1999;Inayat-Hussain et al, 2003;Nasir et al, 2004;Chen et al, 2005;Chan et al, 2006;Al-Qubaisi et al, 2011).…”

“…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). In addition, goniothalamin showed lower toxicity to normal liver Chang cell line as compared to doxorubicin (chemotherapy drug) (Al-Qubaisi et al, 2011). Goniothalamin is a promising antitumor agent against cancerous cell lines (Wattanapiromsakul et al, 2005).…”

“…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).…”

Apoptosis Induction in Human Leukemic Promyelocytic HL-60 and Monocytic U937 Cell Lines by Goniothalamin

“…It is cytotoxic to and induces apoptosis in cancer cells such as cervical cancer (HeLa), breast carcinoma MCF-7 cell lines and colon cancer HT29 cells (Alabsi et al, 2012); Ca9-22 oral cancer cells (Yen et al, 2012); hepatoblastoma HepG2 cells (Al-Qubaisi et al, 2011); human lung cancer cells (Chiu et al, 2011); Jurkat T leukemia cells (Inayat-Hussain et al, 2010); and invasive breast carcinoma MDA-MB231 cell lines (Chen et al, 2005). It is also toxic to normal mouse fibroblast 3T3 cells (Alabsi et al, 2012), coronary artery smooth muscle cells , vascular smooth muscle cells (Chan et al, 2006).…”

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

“…Currently, there are approximately 100 styryl-lactones either discovered from natural products or synthetic analogs. These compounds have been demonstrated to be cytotoxic with prefential killing of cancer cells (Lin and Pihie, 2003;Chen et al, 2005;De Fátima et al, 2006;Al-Qubaisi et al, 2011).…”