Rhein Induces Apoptosis and Cell Cycle Arrest in Human Hepatocellular Carcinoma BEL-7402 Cells

Abstract

Rhein, an anthraquinone derivative of rhubarb, inhibits the proliferation of various human cancer cells. In this paper, we focused on studying the effects of rhein on human hepatocelluar carcinoma BEL-7402 cells and further understanding the underlying molecular mechanism in an effort to make the potential development of rhein in the treatment of cancers. Using MTT assay and flow cytometry, we demonstrate a critical role of rhein in the suppression of BEL-7402 cell proliferation in a concentration- and time-dependent manner. The increase of apoptosis rate was observed after incubation of BEL-7402 cells with rhein at 50-200 muM for 48 hours, and the cells exhibit typical apoptotic features including cellular morphological change and chromatin condensation. Moreover, rhein-induced cell cycle S-phase arrest. Additionally, after rhein treatment, expression levels of c-Myc gene were decreased, while those of caspase-3 gene were increased in a dose-dependent manner by using real-time PCR assay. The results demonstrate for the first time that cell cycle S-phase arrest is one of the mechanisms of rhein in inhibition of BEL-7402 cells. Rhein plays its role by inducing cell cycle arrest via downregulation of oncogene c-Myc and apoptosis through the caspase-dependent pathway. It is expected that rhein will be effective and useful as a new agent in hepatocelluar carcinoma treatment in the future.

Rhein Induces Apoptosis in Human Breast Cancer Cells

“…Results demonstrate that S phase arrest of MCF-7/HER2 cells and increased G1 phase of MCF-7/VEC cells correlated with rhein-induced caspase-9-mediated apoptosis. Rhein-induced S phase arrest of MCF-7/HER2 cells correlates with antiproliferative and apoptotic mechanisms of rhein on human hepatocellular and tongue carcinoma cells [19, 24]. Also, G1 arrest of MCF-7/VEC cells induced by rhein proves consistent with rhein-induced apoptosis of human lung cancer A-549 cells [25] and cervical cancer Ca Ski cells [26].…”

“…The IC50 value of rhein was 36.69 ± 9.77  μ g/mL (129.1 ± 34.37  μ M) for MCF-7/VEC cells and 30.66 ± 2.21  μ g/mL (107.9 ± 7.7  μ M) for MCF-7/HER2 cells. Rhein showed micromolar IC50 values on growth suppression of MCF-7/VEC and MCF-7/HER2 cells, similar to antiproliferative activity of rhein lysinate on human breast cancer cell lines MCF-7, SK-Br-3, and MDA-MB-231 [18] and human hepatocellular carcinoma BEL-7402 cells [19], but less potent than its activity against tongue cancer cell line SCC-4 [20] and ovarian carcinoma cell line SKOV-3 [21]. …”

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

“…ex Balf. ), is potent to inhibit cell growth, induce apoptosis and arrest cell cycle at S phase [140] . Huanglianjiedutang, a classic herbal formula for clearing heat and removing toxicity, was reported to effectively inhibit cell proliferation, induce cell cycle arrest and apoptosis in hepatocarcinoma in vitro and in vivo [141] .…”

Rhein lysinate decreases the generation of β-amyloid in the brain tissues of Alzheimer's disease model mice by inhibiting inflammatory response and oxidative stress

“…Its chemical structure is shown in Figure 1(a). Rhein is a widely used traditional Chinese herb with broad pharmacological effects, including antidiabetic activity [12,13], anti-inflammation, inhibiting interleukin 1 (IL-1) induced chondrocyte activation [14], inhibiting tumor cell proliferation, and inducing tumor cell apoptosis [15,16]. However, because of its water insolubility, the efficacy of rhein was limited in vivo.…”