Huaier aqueous extract induces apoptosis of human fibrosarcoma HT1080 cells through the mitochondrial pathway

Abstract

In recent years, aqueous extract of Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine, has been frequently used in China for complementary cancer therapy. However, the mechanisms underlying its anticancer effects have yet to be elucidated. The present study aimed to evaluate the ability of Huaier extract to inhibit proliferation, promote apoptosis and suppress mobility in the fibrosarcoma HT1080 cell line in vitro. The cells were treated with gradient doses of Huaier extract at concentrations of 0, 4, 8 or 16 mg/ml for 24, 48 or 72 h. The cell viability and motility were measured in vitro using MTT, invasive, migration and scratch assays. The distribution of the cell cycle and the extent of cellular apoptosis were analyzed by flow cytometry. The apoptotic pathways were detected using a mitochondrial membrane potential transition assay and western blotting. The results revealed that the cellular viability decreased significantly with increasing concentrations of Huaier extract. In addition, cell invasiveness and migration were also suppressed significantly. It was demonstrated that Huaier extract induced G2 cell-cycle arrest and cellular apoptosis in a time- and dose-dependent manner. The decreased mitochondrial membrane potential, the downregulation of B-cell lymphoma 2 and pro-caspase-3, and upregulation of Bcl-2-associated X protein, cleaved caspase-9 and caspase-3 suggested that Huaier extract induced the apoptosis of HT1080 cells through the mitochondrial pathway. The results of the present study indicate that Huaier extract is a potential complementary agent for the treatment of fibrosarcoma.

Extensive genomic plasticity identified by anti-cancer Huaier therapy

“…3b). Huaier effects on transcriptional control rescue has been reported before 7,8 , and we frequently identified Hippo signaling pathway 4,.5 , Wnt signaling pathway rescue 22 in the KEGG pathway 24 classification results in the present study. Fig.…”

“…of Huaier 5,[12][13][14][15][16][17][18][19][20][21][22][23] , it should be emphasized the efficacy of Huaier on the significant potential for the recovery from opportunistic virus infections, and also for tissue reproduction to regenerate the damaged tissues and organs after the removal and/or cancer cells in the lesion. The elimination of occult metastasis (after surgical treatment) should be emphasized, too.…”

Huaier restrains proliferative and invasive potential of human hepatoma SKHEP-1 cells partially through decreased Lamin B1 and elevated NOV

“…Huaier has no obvious toxicity and can be used alone or combined with other drugs. Huaier is able to improve the organic immunity, induce apoptosis of cancer cells, and inhibit angiogenesis 9 10 11 12 . However, the mechanisms underlying the anti-cancer effect of Huaier remain elusive.…”

<p><em>Trametes robiniophila</em> Murr: a traditional Chinese medicine with potent anti-tumor effects</p>

“…In cervical cancer, Huaier aqueous extract treatment lead to, through activation of JNK/p38 signaling pathway, G2/M phase arrest 28. This effect of Huaier to induce a G2/M cell cycle arrest has also been proved in studies on gastric cancer cells,29 brosarcoma cells30 and melanoma cells 31. The mechanism may referred to the regulation of the expression of cyclin B1, which binds to Cdc2 to form the complex vital for G2 checkpoint 29…”