Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Taurine Supplementation Ameliorates Arsenic-Induced Hepatotoxicity and Oxidative Stress in Mouse.

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4 mg/L As2O3 via drinking water for 60 days. Group 3, taurine protection group, was treated with 4 mg/L As2O3 and 150 mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.

ETCM: an encyclopaedia of traditional Chinese medicine.

Traditional Chinese medicine (TCM) is not only an effective solution for primary health care, but also a great resource for drug innovation and discovery. To meet the increasing needs for TCM-related data resources, we developed ETCM, an Encyclopedia of Traditional Chinese Medicine. ETCM includes comprehensive and standardized information for the commonly used herbs and formulas of TCM, as well as their ingredients. The herb basic property and quality control standard, formula composition, ingredient drug-likeness, as well as many other information provided by ETCM can serve as a convenient resource for users to obtain thorough information about a herb or a formula. To facilitate functional and mechanistic studies of TCM, ETCM provides predicted target genes of TCM ingredients, herbs, and formulas, according to the chemical fingerprint similarity between TCM ingredients and known drugs. A systematic analysis function is also developed in ETCM, which allows users to explore the relationships or build networks among TCM herbs, formulas,ingredients, gene targets, and related pathways or diseases. ETCM is freely accessible at http://www.nrc.ac.cn:9090/ETCM/. We expect ETCM to develop into a major data warehouse for TCM and to promote TCM related researches and drug development in the future.

Esculentoside A suppresses breast cancer stem cell growth through stemness attenuation and apoptosis induction by blocking IL-6/STAT3 signaling pathway.

Breast cancer stem cells (CSCs) survive in inflammatory microenvironment, their survival are regulated by inflammatory cytokines and signaling pathways. Esculentoside A (EsA), a triterpene saponin derived from the root of Phytolacca esculenta, possesses antiinflammation effects; but whether it has anticancer activity is unknown. The purpose of this study is to test the inhibitory effect of EsA on the growth of breast CSCs and to elucidate its probable mechanisms of action. The proliferation inhibitory effect of EsA on breast CSCs in vitro were determined by cytotoxicity, mammosphere formation inhibition, apoptotic cell detection assays, and in vivo tumor growth inhibition experiment. The possible molecular mechanisms elucidating the inhibitory effect of EsA on breast CSC growth were examined with western blotting. EsA caused proliferation and mammosphere formation inhibition of breast CSCs; induced breast CSCs apoptotic death; suppressed the growth of tumors generated from breast CSCs significantly; the expressions of stemness proteins including ALDH1A1, Sox2, and Oct4 were downregulated; proapoptotic proteins, Bax and cleaved caspase-3 were upregulated, whereas the antiapoptotic protein Bcl-2 was reduced; IL-6/STAT3 pathway proteins including IL-6, phosphorylated STAT3 (Tyr705), and STAT3 (Ser727) were downregulated significantly in EsA-treated breast CSCs and tumor tissues. EsA inhibited breast CSC growth in vitro and in vivo through stemness attenuation and apoptosis induction by blocking IL-6/STAT3 signaling pathway; it might serve as a novel candidate agent for human breast cancer treatment and/or prevention.

Synthesis of 13-amino telekin derivatives and their cytotoxic activity.

Telekin is a eudesmane sesquiterpene-lactone naturally occurring in many medicinal plants with antitumour and anti-inflammatory activity. In this study, a series of 13-amino derivatives of telekin have been synthesised through Michael addition reaction, and their relative configurations were exemplified by the single crystal X-ray diffraction of the dimethylamine adduct. The in vitro cytotoxicity against three tumour cell lines of these amine derivatives was evaluated. The piperidine and 4-hydroxypiperidine adducts displayed stronger cytotoxic activity than telekin.

Lithocarpus polystachyus REHD leaf aqueous extract inhibits human breast cancer growth in vitro and in vivo.

Lithocarpus polystachyus leaves have been used as tea beverage and folk medicine for healthy care in the Southwest of China. The purpose of this study is to investigate the anticancer activity of Lithocarpus polystachyus Rehd leaf aqueous extract (LPAE) and to explore the possible mechanism of its activity. Growth inhibition effects of LPAE breast cancer were tested in vitro and in vivo. The possible mechanism of its activity was analyzed with cell biological and molecular biological assays. After LPAE treatment, the proliferation and colony formation of cancer cells decreased; apoptotic cells increased; DNA fragmentations were evident; mRNA and protein expressions of PPARγ, Bax, and caspase-3 genes increased and expressions of cyclin D1 and Bcl-2 genes decreased; in vivo experiment, LPAE inhibited human beast cancer growth. The findings in this experimental study suggested that LPAE has potential cytotoxic and apoptotic effects on human breast cancer cells in vitro and inhibits the cancer growth in vivo, and its mechanism of activity might be associated with apoptosis induction of cancer cells through upregulation of the mRNA and protein expressions of PPARγ, Bax, and capase-3 genes and downregulation of the expressions of cyclin D1 and Bcl-2 genes.

Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza.

BACKGROUND: Plant natural products have been co-opted for millennia by humans for various uses such as flavor, fragrances, and medicines. These compounds often are only produced in relatively low amounts and are difficult to chemically synthesize, limiting access. While elucidation of the underlying biosynthetic processes might help alleviate these issues (e.g., via metabolic engineering), investigation of this is hindered by the low levels of relevant gene expression and expansion of the corresponding enzymatic gene families. However, the often-inducible nature of such metabolic processes enables selection of those genes whose expression pattern indicates a role in production of the targeted natural product. RESULTS: Here, we combine metabolomics and transcriptomics to investigate the inducible biosynthesis of the bioactive diterpenoid tanshinones from the Chinese medicinal herb, Salvia miltiorrhiza (Danshen). Untargeted metabolomics investigation of elicited hairy root cultures indicated that tanshinone production was a dominant component of the metabolic response, increasing at later time points. A transcriptomic approach was applied to not only define a comprehensive transcriptome (comprised of 20,972 non-redundant genes), but also its response to induction, revealing 6,358 genes that exhibited differential expression, with significant enrichment for up-regulation of genes involved in stress, stimulus and immune response processes. Consistent with our metabolomics analysis, there appears to be a slower but more sustained increased in transcript levels of known genes from diterpenoid and, more specifically, tanshinone biosynthesis. Among the co-regulated genes were 70 transcription factors and 8 cytochromes P450, providing targets for future investigation. CONCLUSIONS: Our results indicate a biphasic response of Danshen terpenoid metabolism to elicitation, with early induction of sesqui- and tri- terpenoid biosynthesis, followed by later and more sustained production of the diterpenoid tanshinones. Our data provides a firm foundation for further elucidation of tanshinone and other inducible natural product metabolism in Danshen.

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

RATIONALE: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes. OBJECTIVE: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes. METHODS AND RESULTS: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption. CONCLUSIONS: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.

Anticancer potential of aqueous extract of alocasia macrorrhiza against hepatic cancer in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Alocasia macrorrhiza has been used as a folk medicine for cancer treatment in the Southwest of China. AIM OF THE STUDY: The purpose of this study is to confirm the anticancer activity of aqueous extract of alocasia macrorrhiza against hepatic cancer and to elucidate its mechanism of action. MATERIALS AND METHODS: Human normal liver cells and hepatocellular carcinoma cells were tested in vitro for cytotoxicity, colony formation inhibition, EdU incorporation, AO/EB staining apoptotic cells, apoptotic DNA fragmentation, and cell cycle distribution in response to alocasia macrorrhiza extract. The mRNA and protein expressions of PPARγ, Cyclin D1, Rb, P21, Bax, Bcl-2 and caspase-3 were detected through RT-PCR and Western blotting; the tumor growth inhibition in vivo was tested by oral administration of the extract. RESULTS: Alocasia macrorrhiza aqueous extract exhibited proliferation inhibition and apoptosis effects on human hepatocellular carcinoma cells in vitro, inhibited hepatoma growth in vivo. CONCLUSION: Alocasia macrorrhiza extract has potential cytotoxic and apoptotic effect on human hepatocellular carcinoma cells and inhibits hepatoma growth in vivo, its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G(0)/G(1)) arrest, apoptosis induction through up-regulation the mRNA and protein expressions of PPARγ, Rb, Bax and capase-3genes and down-regulation of the expressions of Cyclin D1 and Bcl-2 genes.

Growth inhibition and apoptotic effect of alpha-eleostearic acid on human breast cancer cells.

Alpha-eleostearic acid (α-ESA) is a natural and biologically active compound which possesses potent antioxidant and anti-tumor activity. The purpose of this study was to confirm the anticancer activity of α-ESA against human breast cancer cells and to further elucidate its mechanism of activity. Human breast cancer cells and normal liver cells were used for in-vitro tests of the anticancer activity of α-ESA, including cytotoxicity, colony formation inhibition, EdU incorporation, AO/EB staining of apoptotic cells, cell cycle distribution through flow cytometry, and PPARγ, p21, Bax, p53, and caspase-3 mRNA expressions through RT-PCR. After α-ESA treatment, the proliferation, colony formation, and EdU labeling indices of cancer cells decreased (p < 0.05), while the AO/EB-stained apoptotic cells increased (p < 0.05). By FCM analysis, the apoptotic indices increased (p < 0.01), and the cell population decreased in S phase (p < 0.01) and increased in G(2)/M phase (p < 0.05) in α-ESA treated cancer cells. RT-RCR showed that α-ESA significantly increased the expression levels of PPARγ, p21, Bax, p53, and caspase-3 mRNA. The findings in these studies suggested that α-ESA exhibited a potential cytotoxicity and apoptosis induction effect on human breast cancer cells, with little effect on normal cells at certain concentrations. The mechanism for such effects might be associated with the inhibition of DNA synthesis, induction of apoptosis, and cell cycle arrest of cancer cells through up-regulation of PPARγ, p21, Bax, p53, and caspase-3 expressions.

Small RNA profiling in two Brassica napus cultivars identifies microRNAs with oil production- and development-correlated expression and new small RNA classes.

MicroRNAs (miRNAs) and small interfering RNAs are important regulators of plant development and seed formation, yet their population and abundance in the oil crop Brassica napus are still not well understood, especially at different developmental stages and among cultivars with varied seed oil contents. Here, we systematically analyzed the small RNA expression profiles of Brassica napus seeds at early embryonic developmental stages in high-oil-content and low-oil-content B. napus cultivars, both cultured in two environments. A total of 50 conserved miRNAs and 9 new miRNAs were identified, together with some new miRNA targets. Expression analysis revealed some miRNAs with varied expression levels in different seed oil content cultivars or at different embryonic developmental stages. A large number of 23-nucleotide small RNAs with specific nucleotide composition preferences were also identified, which may present new classes of functional small RNAs.

Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells.

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.

Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo.

Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract on human breast cancer in vitro and in vivo, and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation, and gene expression profiling after treatment with LFP extract. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for its anticancer activity and expression of caspase-3 in vivo by oral administration of 0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC(50) = 80 microg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes after LFP water-soluble CEE treatment; the predominantly up-regulated genes were involved in various biological functions including cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, and extracellular matrix/adhesion molecules; and down-regulated genes were mainly associated with adhesion, invasion, and malignancy of cancer cells. A 40.70% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo experiment. The findings in this study suggested that LFP extract might have potential anticancer activity on both ER positive and negative breast cancers, which could be attributed, in part, to its DNA damage effect, proliferating inhibition and apoptosis induction of cancer cells through up-regulation and down-regulation of multiple genes involved in cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, motility and invasiveness of cancer cells; ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)-like 1 (ADPRTL1), Cytochrome P450, subfamily I (CYP1A1) and Hyaluronan-mediated motility receptor (HMMR) might be the main molecular targets at which LFP water-soluble CEE acted.

Potential anticancer activity of litchi fruit pericarp extract against hepatocellular carcinoma in vitro and in vivo.

Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds, and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract against hepatocellular carcinoma in vitro and in vivo, and to elucidate the mechanism of its activity. Human hepatocellular carcinoma cell line was tested in vitro for cytotoxicity, colony formation inhibition, and cell cycle distribution through flow cytometry after treatment with water-soluble crude ethanolic extract (CEE) from LFP. Murine hepatoma bearing-mice were fed doses of 0.15, 0.3, and 0.6g/kg/day of water-soluble CEE in DH(2)O p.o. for 10 days, respectively, to test the anticancer activity and BrdU incorporation of cancer cells in vivo. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cancer cell growth; IC(50) was 80microg/ml, and significantly inhibited colony formation in vitro, tumor growth and BrdU incorporation into cancer cells in vivo. The tumor inhibitory rates at doses of 0.15, 0.3, and 0.6g/kg/day were 17.31% (P>0.05), 30.77% (P<0.05), and 44.23% (P<0.01), respectively. BrdU labeled tumor cells of treated animals were 11.80+/-2.79%, and were significantly lower than that in untreated controls (23.00+/-5.42%, P<0.05). Our findings showed that LFP extract exhibited potential anticancer activity against hepatocellular carcinoma in vitro and in vivo through proliferating inhibition and apoptosis induction of cancer cells.

Potential anticancer activity of tanshinone IIA against human breast cancer.

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic activity against multiple human cancer cell lines, inducing apoptosis and differentiation of some human cancer cell lines. Our purpose was to confirm its anticancer activity on human breast cancer in vitro and in vivo and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation and gene expression profiling after treatment with tanshinone IIA. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for anticancer activity and expression of caspase-3 in vivo by s.c. injection of tanshinone IIA at a dose of 30 mg/kg 3 times/week for 10 weeks. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC50 = 0.25 microg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41 upregulated (1.22%) and 24 downregulated (0.71%) genes after tanshinone IIA treatment. Upregulated genes were involved predominantly in cycle regulation, cell proliferation, apoptosis, signal transduction and transcriptional regulation; and downregulated genes were associated mainly with apoptosis and extracellular matrix/adhesion molecules. A 44.91% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo. Our findings suggest that tanshinone IIA might have potential anticancer activity on both ER-positive and -negative breast cancers, which could be attributed in part to its inhibition of proliferation and apoptosis induction of cancer cells through upregulation and downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis, signal transduction, transcriptional regulation, angiogenesis, invasive potential and metastatic potential of cancer cells. ADPRTL1 might be the main target at which tanshinone IIA acted.

[Alteration of activities of telomerase in tanshinone IIA inducing apoptosis of the leukemia cells].

OBJECTIVE: To investigate the effect of tanshinone IIA on HL-60 and K562 cells apoptosis, and to assay the inhibition of the telomerase activities in the leukemia cell apoptosis induced by Tanshinone. METHOD: Using the techniques of cell culture in vitro, flow cytometry and PCR-TRAP observed the telomerase activities and apoptosis of HL-60 and K562 cells which treated by Tan IIA. RESULT: 0.5 microg x mL(-1) Tan IIA could obviously inhibit HL-60 and K562 cell lines growth (P < 0.05), down-regulate c-myc, bcl-2 gene and up-regulate c-fos and p53 gene expression as well as induce leukemia cell apoptosis, the apoptotic rates of HL-60 and K562 cells were 11.8% and 21.8% respectively. The telomerase activities significant decreased, the inhibiting rates in HL60 and K562 cells were 30.8% and 50.8% respectively. CONCLUSION: Tan IIA could significantly inhibit the proliferation and telomerase activities of HL-60 and K562 cells and induce the leukemia cell apoptosis.

Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells.

AIM: To evaluate the effects of tanshinone II-A on inducing growth inhibition and apoptosis of human hepatocellular carcinoma (HCC) cells. METHODS: The human hepatocellular carcinoma cell line SMMC-7721 was used for the study. The cells were treated with tanshinone II-A at different doses and different times. Cell growth and proliferation were measured by MTT assay, cell count and colony-forming assay. Apoptosis induction was detected by microscopy, DNA ladder electrophoresis and flow cytometry. RESULTS: In MTT assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48, 72 and 96 h after treatment with tanshinone II-A, and the most significant effect was observed at 72 h. On the other hand, the increase of doses (0.125, 0.25, 0.5, 1.0 mg/L tanshinone II-A) resulted in enhanced inhibitory effect. The growth and proliferation of SMMC-7721 cells were obviously suppressed in a dose- and time-dependent manner. The results of cell count were similar to that of MTT assay. In colony-forming assay, the colony-forming rates were obviously inhibited by tanshinone II-A. In tanshinone II-A group, the morphology of cellular growth inhibition and characteristics of apoptosis such as chromatin condensation, crescent formation, margination and apoptotic body were observed under light and transmission electron microscopes. DNA ladder of cells was presented in electrophoresis. The apoptosis index (AI) was 16.9% (the control group was 4.6%) in flow cytometry. The cells were arrested in G(0)/G(1) phase, and the expressions of apoptosis-related genes bcl-2 and c-myc were down-regulated and fas, bax, p53 up-regulated. CONCLUSION: Tanshinone II-A could inhibit the growth and proliferation of HCC cell effectively in vitro by apoptosis induction, which was associated with up-regulation of fas, p53, bax, expression and down-regulation of bcl-2 and c-myc.

[Anticancer effect of tanshinone and its mechanisms].

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, which is a traditional herbal medicine that is used to treat cardiovascular diseases. Recent studies showed that Tanshinone IIA possesses cytotoxic activity against many kinds of human carcinoma cell lines, induces differentiation and apoptosis and inhibits invasion and metastasis of cancer cells. Its mechanisms are thought as inhibiting DNA synthesis and proliferation of cancer cells, regulating the expression of genes related to proliferation, differentiation, and apoptosis, inhibiting the telomerase activity of cancer cells, and changing the expression of cellular surface antigen.