Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3

Abstract

of cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G 1 phase was increased. Flow cytometry assay also showed that ESB had a positive effect on apoptosis. Typical apoptotic morphologies such as condensation and fragmentation of nuclei and blebbing membrane of apoptotic cells could be observed under transmission electron microscope and fluorescence microscope. To further investige the molecular mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their mitochondrial transmembrane potential, released mitochondrial cytochrome C into cytosol, and induced caspase-3 activity in a dose-dependent manner. CONCLUSION: ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells involving loss of mitochondrial transmembrane potential, release of cytochrome C, and activation of caspase-3. INTRODUCTIONScutellaria barbata D.Don (S. barbata) is a perennial herb, also known as Ban-Zhi-Lian (barbat sskullcap) in traditional Chinese medicine. It is mainly distributed in southern China and has been used as an antitumor agent for lung cancer, digestive system cancer, hepatoma, breast cancer, and chorioepithelioma as well as an anti-inflammatory agent and a diuretic in China and Korea [1][2][3][4][5][6][7][8][9] . Extracts from S. barbata (ESB) have in vitro growth inhibitory effects on a number of human cancers including leukemia, colon cancer, hepatoma and skin cancer [4][5][6][7][8][9][10] . However, its antitumor mechanism still remains unclear.It was reported that many Chinese herbs have anticancer properties and induce apoptosis [11] . Three apoptotic pathways have been addressed, including the mitochondrial pathway [12,13] , death receptor pathway [14] , and endoplasmic reticulum stress-mediated apoptosis pathway [15] . The mitochondrial pathway initiates apoptosis in most physiological and pathological situations. Permeabilization outside mitochondrial membrane plays the most important role in mitochondrial apoptosis. In the mitochondria-initiated pathway, mitochondria undergoing permeability transition release apoptogenic proteins such as cytochrome C or apoptosis-inducing factor from the mitochondrial intermembrane space into the cytosol [16] . Released cytochrome C can activate caspase-9, and activated caspase-9 in turn cleaves and activates executioner caspase-3. After caspase-3 activation, some specific substrates for caspase-3 such as poly (ADP-ribose) and polymerase (PARP) are cleaved, and eventually lead to apoptosis [17] . In this study, S. barbata extract showed anti-tumor activity in vitro and could inhibit the growth of mouse H22 hepatoma cells by inhibiting cell apoptosis and cytotoxic effects, demonstrating that the extract from S. barbata can strongly inhibit cell proliferation and induce apoptosis of H22 cells through the mitochondrial dysfunction pathway. MATERIALS AND METHODSReagents and animals N e w b ov i n e s e r u m ( G i b c o, U S A ) , R P M I -1 6 4 0 medium(Gibco, USA), propidium iodide (PI) (Sigma, ...

Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

“…Previous studies have shown that the water and organic solvent extracts of BZL can significantly inhibit the growth of human tumors (Cha et al, 2004;Yin et al, 2004;Goh et al, 2005;Suh et al, 2007;Dai et al, 2008;Kim et al, 2008;Wong et al, 2009). However, limited works have been attempted to elucidate its active components Wu and Chen, 2009).…”

BZL101, a phytochemical extract from theScutellaria barbataplant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype

“…13 One such herb, Scutellaria barbata, known colloquially as Ban Zhi Lian (BZL101), has been shown to have anticancer properties in hepatocarcinoma and leukemia. More specifically, BZL101 is able to induce G 1 cell cycle arrest followed by apoptosis of these cancers 14,15 with effective concentrations of 2 mg/mL and 1 mg/ mL, respectively. Aqueous extracts of BZL101 contain several active anticancer compounds, 16 which are able to block glycolysis and induce cell death in a number of cancer cell lines, 17 and is well tolerated by metastatic breast cancer patients.…”

Protective Effects of Scutellaria barbata Against Rat Liver Tumorigenesis

“…colon cancer, lung cancer, hepatoma, and skin cancer (Yin et al, 2004;Goh et al, 2005;Suh et al, 2007;Dai et al, 2008). Furthermore, our previous research found that CE-SB have antitumor activities both in vitro and in vivo .…”