1.Role of PPAR-γ-regulated autophagy in genistein-induced inhibition of hepatic stellate cell activation.
Xipeng LIU ; Meifang ZHANG ; Haifeng ZHANG ; Anda ZHAO ; Juan SUN ; Wen TANG
Journal of Southern Medical University 2019;39(5):561-565
OBJECTIVE:
To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect.
METHODS:
Cultured HSC-T6 cells were exposed to different concentrations of genistein for 48 h, and HSC activation was verified by detecting the expressions of -SMA and 1(I) collagen; autophagy activation in the cells was determined by detecting the expressions of LC3-II and p62 using Western blotting. The autophagy inhibitor 3-MA was used to confirm the role of autophagy in genistein-induced inhibition of HSC activation. A PPAR-γ inhibitor was used to explore the role of PPAR-γ in activating autophagy in the HSCs.
RESULTS:
Genistein at concentrations of 5 and 50 μmol/L significantly inhibited the expressions of -SMA and 1(I) collagen ( < 0.05), markedly upregulated the expressions of PPAR-γ and the autophagy-related protein LC3-II ( < 0.05) and significantly down-regulated the expression of the ubiqutin-binding protein p62 ( < 0.05) in HSC-T6 cells. The cells pretreated with 3-MA prior to genistein treatment showed significantly increased protein expressions of -SMA and 1(I) collagen compared with the cells treated with genistein only ( < 0.05). Treatment with the PPAR-γ inhibitor obviously lowered the expression of LC3-II and enhanced the expression p62 in genistein-treated HSC-T6 cells, suggesting the activation of the autophagy pathway.
CONCLUSIONS
PPAR-γ- regulated autophagy plays an important role in mediating genistein-induced inhibition of HSC activation .
Anticarcinogenic Agents
;
pharmacology
;
Autophagy
;
Collagen Type I
;
Genistein
;
pharmacology
;
Hepatic Stellate Cells
;
Humans
;
PPAR gamma
;
physiology
2.Pharmacology of mangostins and their derivatives: A comprehensive review.
Ming-Hui WANG ; Kuo-Jun ZHANG ; Qin-Lan GU ; Xiao-Ling BI ; Jin-Xin WANG
Chinese Journal of Natural Medicines (English Ed.) 2017;15(2):81-93
Mangosteen (Garcinia mangostana Linn.) is a well-known tropical tree indigenous to Southeast Asia. Its fruit's pericarp abounds with a class of isoprenylated xanthones which are referred as mangostins. Numerous in vitro and in vivo studies have shown that mangostins and their derivatives possess diverse pharmacological activities, such as antibacterial, antifungal, antimalarial, anticarcinogenic, antiatherogenic activities as well as neuroprotective properties in Alzheimer's disease (AD). This review article provides a comprehensive review of the pharmacological activities of mangostins and their derivatives to reveal their promising utilities in the treatment of certain important diseases, mainly focusing on the discussions of the underlying molecular targets/pathways, modes of action, and relevant structure-activity relationships (SARs). Meanwhile, the pharmacokinetics (PK) profile and recent toxicological studies of mangostins are also described for further druggability exploration in the future.
Animals
;
Anti-Infective Agents
;
pharmacology
;
Anticarcinogenic Agents
;
pharmacology
;
Antineoplastic Agents, Phytogenic
;
pharmacology
;
Antioxidants
;
pharmacology
;
Cardiovascular Agents
;
pharmacology
;
Fruit
;
chemistry
;
Garcinia mangostana
;
chemistry
;
Humans
;
Neuroprotective Agents
;
pharmacology
;
Phytotherapy
;
Plant Extracts
;
pharmacology
;
Protective Agents
;
pharmacology
;
Xanthones
;
pharmacology
3.Cancer Chemoprevention by Ginseng in Mouse Liver and Other Organs.
Hoyoku NISHINO ; Harukuni TOKUDA ; Tsunehiro II ; Manabu TAKEMURA ; Masashi KUCHIDE ; Motohiro KANAZAWA ; Xiao Yang MOU ; Ping BU ; Junko TAKAYASU ; Mari ONOZUKA ; Mitsuharu MASUDA ; Yashiko SATOMI ; Takao KONOSHIMA ; Naoki KISHI ; Masaki BABA ; Yoshihito OKADA ; Toru OKUYAMA
Journal of Korean Medical Science 2001;16(Suppl):S66-S69
Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.
Animal
;
Anticarcinogenic Agents/*pharmacology
;
Female
;
Liver Neoplasms, Experimental/*prevention & control
;
Male
;
Mice
;
Mice, Inbred C3H
;
*Panax
;
Plant Extracts/pharmacology
;
Plant Roots
;
Skin Neoplasms/*prevention & control
4.Antitransforming activity of chlorophyllin against trans-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide.
Wei-Dong JI ; Yi-Guo JIANG ; Min WANG ; Su-Mei FENG
Chinese Journal of Preventive Medicine 2003;37(5):335-337
OBJECTIVETo study the inhibitory effect of chlorophyllin (CHL) on trans-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) induced malignant transformation in human bronchial epithelial cell line (16HBE).
METHODS10, 50 or 100 micro mol/L CHL were added into the media during the cells transformation induced by BPDE, and the malignant degree of transformed cells were identified by the ConA agglutination test and the assay for anchorage-independent growth and tumorigenicity.
RESULTSAfter the cells were cultured for 25 times, the time of cells agglutination in groups treated with both CHL and BPDE was increased significantly; the colony formation efficiency in soft agar in groups treated with both CHL and BPDE (7.4 per thousand, 11.4 per thousand and 14.4 per thousand ) showed significant decrease (P < 0.05) in dose-dependent manner, as compared with that in group treated with BPDE alone (19.6 per thousand ). Cells treated with both CHL and BPDE or BPDE alone developed tumor in nude mice, a squamous carcinoma confirmed by histopathological examination. The volume of tumor in groups treated with both CHL and BPDE (0.43 +/- 0.13) cm(2), (0.22 +/- 0.04) cm(2) and (0.10 +/- 0.06) cm(3) was significantly smaller (P < 0.05) and dose-dependent, as compared with that in the group treated with BPDE alone (1.71 +/- 0.37) cm(3).
CONCLUSIONCHL showed significant antitransforming ability in human bronchial epithelial cell line induced by BPDE.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; toxicity ; Animals ; Anticarcinogenic Agents ; pharmacology ; Cell Transformation, Neoplastic ; drug effects ; Chlorophyllides ; pharmacology ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental ; prevention & control
7.Protective effect of capsaicin against methyl methanesulphonate induced toxicity in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg.
Saba KHANAM ; Ambreen FATIMA ; Rahul Smita JYOTI ; Fahad ALI ; Falaq NAZ ; Barkha SHAKYA ; Yasir Hasan SIDDIQUE
Chinese Journal of Natural Medicines (English Ed.) 2017;15(4):271-280
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, jalapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate (MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.
Acetylcholinesterase
;
metabolism
;
Animals
;
Animals, Genetically Modified
;
Anticarcinogenic Agents
;
pharmacology
;
Capsaicin
;
pharmacology
;
DNA Damage
;
drug effects
;
Drosophila melanogaster
;
drug effects
;
Larva
;
drug effects
;
Methyl Methanesulfonate
;
antagonists & inhibitors
8.Colon Cancer Chemoprevention With Ginseng and Other Botanicals.
Journal of Korean Medical Science 2001;16(Suppl):S81-S86
Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origins. As part of our program on natural products we have examined a number of herbal and botanical products in the aberrant crypt foci (ACF) assay including Korean red ginseng powder, green tea catechins, curcumin from the Indian culinary spice, tumeric, compounds from garlic and onion, resveratrol from red grapes, among others. In the ginseng experiments groups of 10 F344 rats were fed ginseng powder at a dose of 0.5 g/kg or 2 mg/kg for 5 weeks. During weeks 2 and 3 rats were injected with 10 mg/kg azoxymethane to induce ACF. Controls (n=10) did not receive azoxymethane (AOM). Rats were killed by CO2 overdose and ACF counted in the rat colon. In 8 week post-initiation experiments ginseng powder inhibited the progression of established ACF, indicating a cytostatic effect. This may be due to an anti-inflammatory effect. There is a body of literature that suggests that compounds in wine, tumeric, and tea inhibit cyclooxygenases, thus reducing prostaglandin-mediated effects on the colon. As colon tumors have been shown to highly express COX-2 protein, and given, that many NSAID drugs also suppress COX-1, it is tempting to speculate that herbal products that inhibit one or both forms of the COX enzyme will be effective agents for the prevention of cancer in man.
Animal
;
Anticarcinogenic Agents/*pharmacology
;
Colonic Neoplasms/pathology/*prevention & control
;
Disease Models, Animal
;
Human
;
Korea
;
*Panax
;
Precancerous Conditions/pathology/*prevention & control
;
Rats
;
Rats, Inbred F344
9.Effect of tBHQ and sulforaphane on Nrf2-ARE signaling pathway of Caco2 cells.
Xiao-yuan WU ; Li-yan QU ; Kang QUAN ; Yan-ling JIANG ; Xiu-wen TANG
Journal of Zhejiang University. Medical sciences 2010;39(1):17-23
OBJECTIVETo investigate the effect of tBHQ and sulforaphane on the protein expression in Nrf2-ARE signaling pathway of Caco2 cells.
METHODSHuman colorectal carcinoma Caco2 cells were treated with 20 micromol/L tBHQ and 5 micromol/L sulforaphane (SFN) respectively. Real time PCR, Western blotting and immunoflourescence staining (IF) were performed to measure the target gene expression.
RESULTSNrf2, AKR1C1 and NQO1 protein expressions were increased time-dependently in Caco2 cells after treatment with tBHQ and SFN. Time-course experiments showed that tBHQ and SFN increased the accumulation of Nrf2, and concomitantly increased the protein levels of AKR1C1 and NQO1. Real-time PCR and Western blotting showed that tBHQ and SFN significantly increased the expression of Nrf2 at 8h after the treatment, and AKR1C1 and NQO1 at 16 h. Confocal microscopy technique showed that Nrf2 accumulated in the nucleus at 6-8 h after treatment with tBHQ. After 1 h treatment with tBHQ the nuclear Nrf2 maintained at elevated level for at least 4 h with tBHQ withdrawn.
CONCLUSIONtBHQ and SFN induced nuclear accumulation of Nrf2 and activated Nrf2-dependent regulation of ARE-mediated gene expression in Caco2 cells. In addition, the results provide experimental evidence for choosing the dose and frequency of the inducer in cancer chemoprevention study and in developing inhibitors of Nrf2-ARE signaling pathway.
Anticarcinogenic Agents ; pharmacology ; Antioxidants ; metabolism ; pharmacology ; Caco-2 Cells ; Calcium-Transporting ATPases ; antagonists & inhibitors ; Humans ; Hydroquinones ; pharmacology ; Isothiocyanates ; NF-E2-Related Factor 2 ; genetics ; metabolism ; physiology ; Oxidative Stress ; genetics ; physiology ; Response Elements ; physiology ; Signal Transduction ; drug effects ; Thiocyanates ; pharmacology
10.Resveratrol inhibits EGF-induced invasion of human lung adenocarcinoma A549 cells.
Ningyu HUANG ; Hong LU ; Lijun CHANG ; Hongwei ZHANG ; Hao ZHANG ; Guanwu LI
Chinese Journal of Lung Cancer 2010;13(4):287-291
BACKGROUND AND OBJECTIVEInvasion and metastasis are the primary causes of death in patients with pulmonary carcinoma. The epidermal growth factor (EGF) stimulates A549 cells invasion greatly through activating ERK and PI3K-Akt signaling pathway. The aim of this study is to elucidate the inhibitory effect of Resveratrol on EGF-induced invasive ability of A549 cells in vitro and explore the molecular mechanism.
METHODSThe cytotoxicity of Resveratrol was evaluated by methyl thiazolyltetrazolium (MTT) assay. Then, the A549 cells were treated with EGF and non-cytotoxic concentration of Resveratrol. The cells' invasion were detected by Boyden chamber assay; MMP-2 activity was determined by gelatine zymography assay; the changes of the related proteins were detected by Western blot.
RESULTSResveratrol was not toxic to A549 cells at the concentration between 0 to 30 microM. The invasion ability of EGF-induced A549 cells was decreased after treatment with 20 microM resveratrol for 24 h, accompanied by the inhibition of MMP-2 secretion. And the levels of p-ERK1/2, PI3K (within 6 h) were suppressed too.
CONCLUSION20 microM Resveratrol inhibits A549 cells' invasion possibly through the suppression of the activation of ERK and PI3K-Akt signaling pathways, subsequently exerting inhibitory effect on MMP-2.
Adenocarcinoma ; metabolism ; Anticarcinogenic Agents ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Epidermal Growth Factor ; pharmacology ; Humans ; Lung Neoplasms ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; drug effects ; Stilbenes ; pharmacology