Signal pathways in the treatment of Alzheimer's disease with traditional Chinese medicine.

AIM OF THE REVIEW: This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), and provide support for further investigation on TCM and its active ingredients. MATERIALS AND METHODS: Literature survey was conducted using PubMed, Web of Science, Google Scholar, CNKI, and other databases, with "Alzheimer's disease," "traditional Chinese medicine," "medicinal herb," "Chinese herb," and "natural plant" as the primary keywords. RESULTS: TCM could modulate signal pathways related to AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, and PI3K/Akt/mTOR, as well as SIRT1 and PPARα pathway. It could regulate crosstalk between pathways through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating ubiquitin-proteasome system function, modulating autophagy, and eventually improving cognitive impairment in patients with AD. CONCLUSION: TCM could be multilevel, multitargeted, and multifaceted to prevent and treat AD. In-depth research on the prevention and treatment of AD with TCM could provide new ideas for exploring the pathogenesis of AD and developing new anti-AD drugs.

Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

BACKGROUND: Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. METHODS: The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. RESULTS: A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and ß-sitosterol were obtained from the analysis of the key targets. CONCLUSIONS: Ursolic acid, anethole and ß-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.

α­Solanine inhibits growth and metastatic potential of human colorectal cancer cells.

Solanum nigrum L. (Longkui) is one the most widely used anticancer herbs in traditional Chinese medicine. α­Solanine is an important ingredient of S. nigrum L. and has demonstrated anticancer properties in various types of cancer. However, the effects of α­solanine on colorectal cancer remain elusive. The aim of the present study was to assess the effects of α­solanine on human colorectal cancer cells. The results demonstrated that α­solanine inhibited the proliferation of RKO cells in a dose­ and time­dependent manner. In addition, α­solanine arrested the cell cycle at the G0/G1 phase and suppressed the expression levels of cyclin D1 and cyclin­dependent kinase 2 in RKO cells. α­Solanine induced apoptosis of RKO cells, as indicated by morphological changes and positive Annexin­FITC/propidium iodide staining. Additionally, α­solanine activated caspase­3, ­8 and ­9 in RKO cells, which contributed to α­solanine­induced apoptosis. α­Solanine also increased the generation of reactive oxygen species, which contributed to caspase activation and induction of apoptosis. α­Solanine inhibited the migration, invasion and adhesion of RKO cells, as well as the expression levels and activity of matrix metalloproteinase (MMP)­2 and MMP­9. In addition, α­solanine inhibited cell proliferation, activated caspase­3, ­8 and ­9, induced apoptosis, and inhibited the migration and invasion of HCT­116 cells. Furthermore, α­solanine inhibited tumor growth and induced apoptosis in vivo. These findings demonstrated that α­solanine effectively suppressed the growth and metastatic potential of human colorectal cancer.

Chinese medicine Di-Huang-Yi-Zhi protects PC12 cells from H2O2-induced apoptosis by regulating ROS-ASK1-JNK/p38 MAPK signaling.

BACKGROUND: Oxidative stress mediates the nerve injury during the pathogenesis of Alzheimer's disease (AD). Protecting against oxidative stress damage is an important strategy to prevent and treat AD. Di-Huang-Yi-Zhi (DHYZ) is a Chinese medicine used for the treatment of AD, but its mechanism remains unknown. This study is aimed to investigate the effect of DHYZ on H2O2 induced oxidative damage in PC12 cells. METHODS: PC12 cells were treated with H2O2 and DHYZ. Cell proliferation was detected by Cell counting kit-8 (CCK-8) assay. Cytotoxicity of H2O2 was measured by lactate dehydrogenase (LDH) release assay. Apoptosis were identified by Annexin V-FITC/PI staining. Caspase 3 activity was detected by commercial kit. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Reactive oxygen species (ROS) was 2', 7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. RESULTS: The results showed that DHYZ antagonized H2O2-mediated cytotoxicity and proliferation inhibition. DHYZ reduced ROS production, stabilize mitochondrial membrane potential, inhibit Caspase-3 activity and apoptosis induced by H2O2. In addition, DHYZ inhibited the phosphorylation of ASK1, JNK1/2/3 and p38 MAPK which were up-regulated by H2O2. CONCLUSIONS: The present study suggested that DHYZ protected PC12 cells from H2O2-induced oxidative stress damage and was related to inhibition of ROS production and ASK1-JNK/p38 MAPK signaling. The present study provides experimental evidence for the application of DHYZ for the management of oxidative stress damage and AD.

Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-ß1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a vital process in cancer progression and metastasis. Yanggan Jiedu Sanjie (YGJDSJ) is Traditional Chinese Medicine formulation for liver cancer treatment. In the present study, we evaluated the effects of YGJDSJ on TGF-ß1-induced EMT in hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were treated with TGF-ß1 and YGJDSJ. EMT was identified by morphological changes and expression of marker proteins. Cell morphology was observed under a microscope. Protein expression and phosphorylation was detected by western blotting. Cell migration was measured by the scratch assay. Cell adhesion and invasion was detected by a commercial kit. RESULTS: YGJDSJ reversed TGF-ß1-induced morphological changes, as well as the expression of the EMT markers E-cadherin and N-cadherin in Bel-7402 cells. YGJDSJ also inhibited TGF-ß1 up-regulated Smad3 phosphorylation and Snail expression in Bel-7402 cells. Moreover, YGJDSJ inhibited TGF-ß1-induced cell adhesion, migration and invasion in Bel-7402 cells. CONCLUSIONS: YGJDSJ inhibited TGF-ß1-induced EMT and mediated metastatic potential of Bel-7402 cells, which may be related to down-regulation of Smad3 phosphorylation and Snail expression. The present study provides a new basis for application of this herbal formula for prevention of liver cancer metastasis.

Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis in hepatocellular carcinoma Bel-7402 cells.

BACKGROUND: Based on clinical medications and related studies, we established a Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment. In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension-grown human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and treated with YGJDSJ. Anchorage-independent cell growth was detected by cell Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis. Caspases activities were detected by the cleavage of chromogenic substrate. Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402 cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8 and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated YGJDSJ induced anoikis. CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS generation and PTK2 downregulation.

Teng-Long-Bu-Zhong-Tang induces p21-dependent cell senescence in colorectal carcinoma LS174T cells via histone acetylation.

Teng-Long-Bu-Zhong-Tang (TLBZT) is a Chinese herbal formula for colorectal carcinoma treatment. TLBZT effectively induces cell senescence in colorectal carcinoma, accompanied by p21 upregulation. In this study, we further explored the role of p21 in TLBZT-induced cell senescence, as well as the mechanism by which TLBZT upregulates p21. Specific knockdown of p21 expression by small interfering RNA significantly attenuated TLBZT-induced cell senescence in human colorectal carcinoma LS174T cells. Silencing of p53 by small interfering RNA did not affect TLBZT-induced p21 upregulation. Meanwhile, TLBZT inhibited histone deacetylase activity. Furthermore, TLBZT increased acetylation levels of histone H3 and H4, enhancing their binding to the p21 promoter. These data suggested that TLBZT induces cell senescence in LS174T cells through a mechanism involving p21 upregulation via histone H3 and H4 acetylation. This study provides new insights into the application of TLBZT for colorectal carcinoma treatment.

Di-Huang-Yi-Zhi herbal formula attenuates amyloid-ß-induced neurotoxicity in PC12 cells.

Traditional Chinese medicine can be used for Alzheimer's disease management, such as the modern herbal formula Di-Huang-Yi-Zhi (DHYZ). In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of DHYZ against amyloid-ß peptide 25-35 (Aß25-35) induced neurotoxicity, particularly regarding cell proliferation, apoptosis and related events. Following treatment with DHYZ, cell viability, cell membrane damage, apoptosis, mitochondrial membrane potential, cytochrome c release, caspase-3 activity and levels of reactive oxygen species in PC12 cells were detected. The results demonstrated that pretreatment with DHYZ significantly protected PC12 cells from Aß25-35-induced proliferation inhibition, lactate dehydrogenase release and apoptosis, as well as upregulating mitochondrial membrane potential and downregulating cytochrome c release and caspase-3 activation. DHYZ also inhibited the Aß25-35-induced reactive oxygen species generation in PC12 cells. These observations suggest that DHYZ protected PC12 cells from the Aß-induced neurotoxicity.

Herbal compound Teng-Long-Bu-Zhong-Tang inhibits metastasis in human RKO colon carcinoma.

Metastasis is one of the primary obstacles to the successful treatment of colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal formula that may be useful in the treatment of metastatic colorectal cancer. The present study evaluated the effects of TLBZT on lung metastasis in human RKO colon carcinoma cells injected into mice via the tail vein. The results demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia-inducible factor 1α. TLBZT also inhibited the expression of integrins αV and ß3 and the phosphorylation of focal adhesion kinase. These results indicate that TLBZT inhibits the lung metastasis of RKO colon carcinoma by regulating the expression of multiple genes. The results of the present study provide a new basis for the management of colorectal cancer metastasis using treatments derived from Chinese herbs.

Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma.

Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.

Secondary metabolites of plants from the genus chloranthus: chemistry and biological activities.

Chloranthus, a genus of the family Chloranthaceae, which is mainly distributed in eastern and southern Asia, has been used in Chinese folk medicine due to its antitumor, antifungal, and anti-inflammatory activities. This review compiles the research on isolation, structure elucidation, structural diversity, and bioactivities of Chloranthus secondary metabolites reported between 2007 and 2013. The metabolites listed encompass 82 sesquiterpenoids, 50 dimeric sesquiterpenoids, 15 diterpenoids, one coumarin, and five other compounds. Among them, dimeric sesquiterpenoids, the characteristic components of plants from the genus Chloranthus, have attracted considerable attention due to their complex structures and significant biological features, e.g., antitumor, antibacterial, antifungal, anti-inflammatory, and hepatoprotective activities, and potent and selective inhibition of the delayed rectifier (IK) K(+) current and tyrosinase.

Ligustrum lucidum Ait. fruit extract induces apoptosis and cell senescence in human hepatocellular carcinoma cells through upregulation of p21.

Nü-zhen-zi, the fruit of Ligustrum lucidum Ait., is one of the most frequently used liver Yin tonifying Chinese herbs for the treatment of liver cancer. However, the effect of Ligustrum lucidum fruit on hepatocarcinoma cells remains unknown. In the present study, we evaluated the effects of a Ligustrum lucidum fruit extract (LLFE) on human hepatocellular carcinoma Bel-7402 cells. The results showed that LLFE inhibited the proliferation of the Bel-7402 cells in a dose- and time-dependent manner. LLFE induced apoptosis in Bel-7402 cells accompanied by activation of caspase-3, -8 and -9. LLFE-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. LLFE treatment also caused a large and flat morphologic cellular change, positive SA-ß-gal staining, and G0/G1 phase cell cycle arrest in the Bel-7402 cells, accompanied by upregulation of p21 and downregulation of RB phosphorylation. Specific knockdown of p21 expression by RNA interference partially abrogated LLFE-induced apoptosis, and significantly abrogated LLFE-induced cell senescence. These observations suggest that Nü-zhen-zi is a potential anticancer herb and support the traditional use of Nü-zhen-zi for hepatocarcinoma treatment.

Acorus tatarinowii Schott extract protects PC12 cells from amyloid-beta induced neurotoxicity.

Amyloid-beta induced neurotoxicity has been identified as a major cause of Alzheimer's disease. Acorus tatarinowii Schott is one of the most frequently used Chinese herbs for Alzheimer's disease treatment. However, the effects of Acorus tatarinowii Schott on amyloid-beta mediated nerve cell damage remains unknown. In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of A. tatarinowii Schott extract (ATSE) against Abeta25-35 induced neurotoxicity. The results showed pretreatment with ATSE significantly protected PC12 cells from Abeta25-35 induced cell death, lactate dehydrogenase release, DNA damage, mitochondrial dysfunction and cytochrome c release from mitochondria. In addition, pretreatment with ATSE also significantly inhibited Abeta25-35 induced caspase-3 activation and reactive oxygen species generation in PC12 cells. These observations suggested that ATSE protects PC12 cells from amyloid-beta induced neurotoxicity.

Teng-Long-Bu-Zhong-Tang, a Chinese herbal formula, enhances anticancer effects of 5--Fluorouracil in CT26 colon carcinoma.

BACKGROUND: Colorectal cancer remains one of the leading causes of cancer death worldwide. Traditional Chinese Medicine (TCM) has played a positive role in colorectal cancer treatment. There is a great need to establish effective herbal formula for colorectal cancer treatment. Based on TCM principles and clinical practices, we have established an eight herbs composed formula for colorectal cancer treatment, which is Teng-Long-Bu-Zhong-Tang (TLBZT). We have demonstrated the anticancer effects of TLBZT against colorectal carcinoma in vitro. In present study, we evaluated the anticancer potential of TLBZT, used alone or in combination with low dose of 5-Fluorouracil (5-Fu), in CT26 colon carcinoma in vivo. METHODS: CT26 colon carcinoma was established in BALB/c mice and treated with TLBZT, 5-Fu, or TLBZT plus 5-Fu. The tumor volumes were observed. Apoptosis was detected by TUNEL assay. Caspases activities were detected by colorimetric assay. Cell senescence was indentified by senescence ß-galactosidase staining. Gene expression and angiogenesis was observed by immunohistochemistry or western blot. RESULTS: TLBZT significantly inhibited CT26 colon carcinoma growth. TLBZT elicited apoptosis in CT26 colon carcinoma, accompanied by Caspase-3, 8, and 9 activation and PARP cleavage, and downregulation of XIAP and Survivin. TLBZT also induced cell senescence in CT26 colon carcinoma, with concomitant upregulation of p16 and p21 and downregulation of RB phosphorylation. In addition, angiogenesis and VEGF expression in CT26 colon carcinoma was significantly inhibited by TLBZT treatment. Furthermore, TLBZT significantly enhanced anticancer effects of 5-Fu in CT26 colon carcinoma. CONCLUSIONS: TLBZT exhibited significantly anticancer effect, and enhanced the effects of 5-Fu in CT26 colon carcinoma, which may correlate with induction of apoptosis and cell senescence, and angiogenesis inhibition. The present study provides new insight into TCM approaches for colon cancer treatment that are worth of further study.

Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine.

[Effect of Solanum nigrum on human colon carcinoma RKO cells ].

OBJECTIVE: To evaluate the effect of Solanum nigrum on adhesion, migration and invasion in human colon carcinoma RKO cells. METHODS: RKO cells were treated with different dose of Solanum nigrum. Cell proliferation was detected by CCK-8 assay. Cell adhesion was observed with CytoSelect 48-Well Cell Adhesion Assay. Cell migration was detected with scratch assay. Cell invasion was analyzed by CytoSelect 24-Well Cell Invasion Assay. RESULTS: At final concentration of 400-1600 microg/mL, Solanum nigrum significantly inhibited proliferation of RKO cells in a dose-dependent manner. At final concentration of 100-400 microg/mL, Solanum nigrum significantly inhibited adhesion,migration and invasion in RKO cells. CONCLUSION: Solanum nigrum may inhibit the proliferation, adhesion, migration and invasive abilities in RKO cells. The present study provides new insight into the application of Solanum nigrum for colon carcinoma treatment that are worthy of further study.

Liver Yin deficiency tonifying herbal extract induces apoptosis and cell senescence in Bel-7402 human hepatocarcinoma cells.

Liver cancer ranks as the fifth most prevalent malignancy of all cancers worldwide. According to the principles of traditional Chinese medicine, liver Yin deficiency is a common clinical syndrome of liver cancer, and tonifying liver Yin is a common treatment method for liver cancer. However, no hepatocarcinoma-specific liver Yin tonifying formula has yet been established. In the present study, we established a liver cancer-specific combination of herbs, which we term liver Yin tonifying formula (LYTF). We found that LYTF inhibits the proliferation of Bel-7402 cells in a dose- and time-dependent manner. LYTF induces apoptosis in Bel-7402 cells, which is accompanied by activation of caspases-8, -9 and -3. Pan-caspase blocking completely abrogates LYTF-induced apoptosis and partially abrogates LYTF-induced proliferation inhibition. LYTF also induces cell senescence, as indicated by a large and flattened morphology, senescence-activated ß-galactosidase-positive staining and G0/G1 cell cycle arrest, accompanied by the up-regulation of p16 and p21 and the down-regulation of retinoblastoma protein phosphorylation. These findings suggest that LYTF is effective in inhibiting the growth and survival of hepatocarcinoma cells through the induction of apoptosis and cell senescence. Our study also provides insight into traditional Chinese medicine methods used for the treatment of liver cancer.

Polygonum cuspidatum Extract Induces Anoikis in Hepatocarcinoma Cells Associated with Generation of Reactive Oxygen Species and Downregulation of Focal Adhesion Kinase.

Anoikis has been recognized as a potential target for anticancer therapy. Polygonum cuspidatum (Huzhang) is a frequently used Chinese herb in hepatocarcinoma. In present study, we evaluated the effects of Polygonum cuspidatum extract (PCE) in hepatocarcinoma cells in suspension. The results showed that PCE inhibited the proliferation of hepatocarcinoma cells in suspension in a dose- and time-dependent manner. PCE also inhibited anchorage-independent growth of hepatocarcinoma cells in soft agar. PCE induced anoikis in human hepatocarcinoma Bel-7402 cells accompanied by caspase-3 and caspase-9 activation and poly(ADP-ribose) polymerase cleavage, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. In addition, PCE treatment induced intracellular reactive oxygen species (ROS) production in Bel-7402 cells. NAC, an ROS scavenger, partially attenuated PCE-induced anoikis and activation of caspase-3 and caspase-9. Furthermore, PCE inhibited expression of focal adhesion kinase (FAK) in Bel-7402 cells. Overexpression of FAK partially abrogated PCE-induced anoikis. These data suggest that PCE may inhibit suspension growth and induce caspase-mediated anoikis in hepatocarcinoma cells and may relate to ROS generation and FAK downregulation. The present study provides new insight into the application of Chinese herb for hepatocarcinoma treatment.

Modified Yi Guan Jian, a Chinese herbal formula, induces anoikis in Bel-7402 human hepatocarcinoma cells in vitro.

Liver cancer is the fifth most common malignancy worldwide. Liver YIN deficiency is a common clinical syndrome of traditional Chinese medicine in liver cancer. Yi Guan Jian is an ancient classic liver YIN tonifying herbal formula used for the treatment of liver disease with liver YIN deficiency, which is also currently used for liver cancer treatment. However, as an ancient formula, Yi Guan Jian (YGJ) is not entirely suitable for liver cancer treatment. In the present study, we optimized the prescription of YGJ according to the current principles of Chinese herbal medication, and evaluated the anticancer effects of modified Yi Guan Jian (MYGJ) in Bel-7402 human hepatocarcinoma cells. The results show that MYGJ inhibited the growth of Bel-7402 cells in adherent or in suspension cultures, and was more effective in Bel-7402 cells in suspension. MYGJ also inhibited anchorage-independent growth of Bel-7402 cells in soft agar. MYGJ induced anoikis in Bel-7402 cells accompanied by caspase-3, -8 and -9 activation, which was blocked by the pan-caspase inhibitor, Z-VAD-FMK. Furthermore, MYGJ inhibited the expression and phosphorylation of p38 MAPK in Bel-7402 cells. These findings suggest that MYGJ is sufficient to induce caspase-mediated anoikis in Bel-7402 cells in vitro, and may be associated with down-regulation of p38 MAPK. The present study also provides insight into the application of ancient Chinese herbal formulas.

Aqueous extract of Curcuma aromatica induces apoptosis and G2/M arrest in human colon carcinoma LS-174-T cells independent of p53.

Curcuma aromatica is a common Chinese herb for treating diseases with blood stasis and has been regarded as an anticancer herb in modern clinical practice. However, the anticancer effects and related molecular mechanisms of Curcuma aromatica remain unclear. In the present study, human colon carcinoma LS-174-T cell line with wild-type p53 was used as a model cell to evaluate the anticancer effects of aqueous extract of Curcuma aromatica (AECA). AECA inhibits LS-174-T cell proliferation in a dose- and time-dependent manner and colony formation in a dose-dependent manner. AECA treatment induces apoptosis accompanied by caspase-8, -9, and -3 activation in LS-174-T cells. Moreover, blocking the activities of these caspases with a specific inhibitor significantly protected LS-174-T cells from AECA-induced apoptosis. AECA treatment also induces G2/M phase arrest in LS-174-T cells. Expression of p53 was unchanged after AECA treatment; specific silence of p53 did not influence AECA-induced apoptosis and G2/M phase arrest. Further, the expression of cyclin B1 and CDK1 was reduced by AECA. This study suggests that AECA might be effective as an antiproliferative herb for colon carcinoma, the antitumor activity of AECA may involve both extrinsic and intrinsic apoptosis, and AECA induces G2/M phase arrest via downregulation of cyclin B1 and CDK1 and without the participation of p53.