clove and Liver-Neoplasms

Lemon myrtle (Backhousia citriodora F.Muell.) leaves, whether fresh or dried, are used traditionally in folk medicine to treat wounds, cancers, skin infections, and other infectious conditions. However, the targets and mechanisms related to anti-cancer effect of lemon myrtle are unavailable. In our study, we found that the essential oil of lemon myrtle (LMEO) showed anti-cancer activity in vitro, and we initially explored its mechanism of action.. We analyzed the chemical compositions of LMEO by GC-MS. We tested the cytotoxicity of LMEO on various cancer cell lines using the MTT assay. Network pharmacology was used also to analyze the targets of LMEO. Moreover, the mechanisms of LMEO were investigated through scratch assay, flow cytometry analysis, and western blot in the HepG2 liver cancer cell line.. LMEO showed cytotoxicity in various cancer cell lines in vitro. Pharmacological networks showed LMEO to have multi-component and multi-targeting effects that are related to inhibit migration of HepG2 cells, and affect cell cycle S-phase arrest and apoptosis through modulation of p53 protein.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cyclins; Hep G2 Cells; Humans; Liver Neoplasms; Lung Neoplasms; Myrtaceae; Myrtus; Neuroblastoma; Oils, Volatile; Tumor Suppressor Protein p53

Hepatocellular carcinoma (HCC) arising from fibrosis/cirrhosis is the most common type of primary liver cancer. Conversely, a higher intake of fruits and vegetables might play a protective role in HCC risk. Recently, Myrtaceae family tropical fruits have raised great interest due to the high levels of anthocyanins especially in their peels, which are usually discarded upon consumption. Anthocyanins are antioxidant pigments known to have beneficial effects in vivo/in vitro cancer bioassays. Thus, we evaluated whether dietary Myrciaria jaboticaba, Syzygium cumini, and Syzygium malaccense fruit peel powders reduce fibrosis and hepatocarcinogenesis in mice. Female C3H/HeJ mice were submitted to the model of diethylnitrosamine/carbon tetrachloride-induced liver fibrosis and carcinogenesis. Concomitantly, mice received a basal diet containing 2% of M. jaboticaba, S. cumini, or S. malaccense fruit peel powders, obtained by convective drying, for 10 weeks. M. jaboticaba peel powder showed the highest levels of total anthocyanins, while S. cumini peel powder displayed the greatest diversity of these pigments. All Myrtaceae family peel powders reduced the serum levels of the liver injury marker alanine aminotransferase. M. jaboticaba peel feeding reduced the incidence of liver preneoplastic foci, hepatocyte proliferation (Ki-67), and the protein levels of hepato-mitogen tumor necrosis factor-alpha (TNF-α). M. jaboticaba peel feeding also diminished liver lipid peroxidation and increased total glutathione levels. S. cumini peel feeding reduced hepatic collagen, lipid peroxidation, and TNF-α levels while increased catalase activity. Although S. malaccense peel powder, which displayed the lowest anthocyanin levels, decreased oxidative stress, and cytokine levels, no effects were observed on liver fibrosis or preneoplastic lesion outcomes. Findings indicate a protective effect of anthocyanin-rich M. jaboticaba and S. cumini peel powder feeding on preneoplastic lesion development and fibrosis, respectively. Results indicate that differential biological responses may be attributed to distinct anthocyanin profiles and levels, assigning a functional/market value to the underutilized peel fraction.

Topics: Animals; Anthocyanins; Carcinogenesis; Carcinoma, Hepatocellular; Female; Fruit; Liver Cirrhosis; Liver Neoplasms; Mice; Mice, Inbred C3H; Myrtaceae

Syzygium cumini (Myrtaceae) is commonly called as Jamun or Jambolan. It has antidiabetic, anti-inflammatory, antipyretic, and antioxidant activities. Hepatocellular carcinoma is the most frequent and deadliest cancers worldwide. We investigated the cytotoxic potentials of S. cumini methanolic seed kernel extract against human hepatoma HepG2 cells. HepG2 cells were treated with 10, 20, and 40 μg/mL of seed kernel extract for 24 hours and cytotoxic analysis was performed by MTT assay. S. cumini induced apoptosis related morphological changes in HepG2 cells were analyzed by annexin V and propidium iodide double staining. Nuclear fragmentation and chromatin condensation were analyzed by Hoechst nuclear staining. Mitochondrial membrane potential (MMP) was investigated by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) staining. Protein expressions of hepatocyte nuclear factor-1α (HFN-1α) was performed using western blotting. S. cumini treatments caused a significant and a concentration-dependent increase in the cytotoxicity of HepG2 cells. S. cumini treatments increased the percentage of cells in an early and late apoptosis stage. This treatment also caused chromatin condensation and nuclear fragmentation. Further, S. cumini treatments decreased MMP and also caused a significant downregulation of HFN-1α protein expression. The present study demonstrated that S. cumini seed extract induced apoptosis in HepG2 cells through decrease in MMP and downregulation of HFN-1α.

Topics: Apoptosis; Carcinoma, Hepatocellular; Down-Regulation; Hep G2 Cells; Hepatocyte Nuclear Factor 1-alpha; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Methanol; Myrtaceae; Plant Extracts; Seeds

Callistemon lanceolatus (Myrtaceae) has been utilized in folk medicine and its pharmacological properties are widely studied. Phytochemicals are effectively recognized as bases of pharmacologically potent drugs for the development of anticancer therapeutics. The free radical scavenging potential of numerous extracts of C. lanceolatus leaves, Hexane leaf extract (HLE), Chloroform leaf extract (CLE), Ethyl acetate leaf extract (ELE), Methanol leaf extract (MLE), and Aqueous leaf extract (ALE)) were determined by Biochemical assay. We evaluated the anticancer activity of C. lanceolatus leaves extracts against different human cancer cell lines viz liver cancer cells (HepG2), breast cancer cells (MCF7), and normal human embryonic kidney (HEK 293) cell line. The ELE and MLE extracts of C. lanceolatus leaves showed potential antiproliferative effects on HepG2 cells. On the basis of free radical scavenging potential and cytotoxicity studies, ELE and MLE extracts of C. lanceolatus leaves are further evaluated in detail for numerous biological activities. ELE and MLE extracts reduced the cell growth, ROS generation, lowering the potential of cell migration and inhibits the metastatic activity in HepG2 cell lines. ELE and MLE extracts treated HepG2 cells showed down-regulation of STAT3 and up-regulation of p53 and inhibition of cdk2 and cyclin A activity. Phytochemicals analysis have shown that the ELE and MLE possess some anticancer compounds like 4-Fluoro-2-trifluoromethylbenzoic acid, neopentyl ester; fumaric acid, di(pent-4-en-2-yl) ester; 2,3-Dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one and 2-Furancarboxaldehyde,5-(hydroxymethyl). Molecular docking results demonstrate that interactions of compounds present in ELE and MLE extracts with the SH2 domain of STAT3, might be responsible for their inhibitory effects. We have further concluded that the ELE and MLE extracts of C. lanceolatus arrests the cells at S and G2/M phase and subsequently induced cell death by regulating the DNA damage in HepG2 cells.

Topics: Acetates; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Movement; Cell Proliferation; DNA Damage; Dose-Response Relationship, Drug; HEK293 Cells; Hep G2 Cells; Humans; Liver Neoplasms; MCF-7 Cells; Methanol; Molecular Docking Simulation; Myrtaceae; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Protein Binding; Signal Transduction; Solvents; src Homology Domains; STAT3 Transcription Factor; Structure-Activity Relationship; Tumor Suppressor Protein p53

B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels. Using this screening assay, the methanol-soluble extracts of Beaumontia murtonii and Eugenia operculata were selected as leads. Bioassay-guided fractionation of the extracts led to the isolation of three known cardenolides (1-3) and one new compound (4) from B. murtonii and two known triterpenoids (5 and 6) and one new compound (7) from E. operculata. These seven compounds inhibited BMI1 promoter activity (IC

Topics: Animals; Antineoplastic Agents; Apocynaceae; Blotting, Western; Carcinoma, Hepatocellular; Cardenolides; Cell Line, Tumor; Eugenia; HCT116 Cells; HEK293 Cells; Humans; Inhibitory Concentration 50; Liver Neoplasms; Mice; Molecular Structure; Neoplastic Stem Cells; Plant Leaves; Polycomb Repressive Complex 1; Thailand; Triterpenes

Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its reversal effects on cancer cell MDR.. A human hepatocellular tumor xenograft model was established with the BEL-7402/5-FU cell line. Combined 5-fluorouracil (5-FU) and DMC (40 mg kg(-1) ) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor tissues and increase caspase-3 activity. Also, combined therapy resulted in enhanced tumor apoptotic and reduced proliferative activities relative to 5-FU alone. Examining body weight and other signs of unwanted toxicity of the different treatment groups revealed no significant signs of adverse effects.. All results suggested that DMC reverses 5-FU resistance, with a benign side effects profile.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; Chalcones; Disease Models, Animal; Drug Resistance, Multiple; Female; Fluorouracil; Humans; Liver Neoplasms; Meristem; Mice; Mice, Inbred BALB C; Mice, Nude; Myrtaceae; Phytotherapy; Plant Extracts; Transplantation, Heterologous; Xenograft Model Antitumor Assays

Previously we have shown that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated from the buds of Cleistocalyx operculatus, significantly inhibits the growth of human liver cancer SMMC-7721 cells and is able to induce apoptosis of SMMC-7721 cells in vitro. Here we report the antitumor effects of DMC in vivo, using a solid human tumor xenograft mouse model using human liver cancer SMMC-7721 cells. The average tumor weights in the control group and in mice injected with 150 mg/kg DMC were 1.42+/-0.11 g and 0.59+/-0.12 g, respectively. Flow cytometric analysis of the tumor cell population demonstrated an aneuploid peak (representing 33.60+/-0.80% of the total in mice injected with 150 mg/kg DMC). To our knowledge, this is the first time that chalcone compounds have been applied to a human tumor xenograft model.

Topics: Animals; Carcinoma; Chalcone; Chalcones; Disease Models, Animal; Drug Screening Assays, Antitumor; Liver Neoplasms; Mice; Myrtaceae; Plant Extracts; Transplantation, Heterologous

The antimicrobial and toxicological properties of the Australian essential oil, lemon myrtle, (Backhousia citriodora) were investigated. Lemon myrtle oil was shown to possess significant antimicrobial activity against the organisms Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, methicillin-resistant S. aureus (MRSA), Aspergillus niger, Klebsiella pneumoniae and Propionibacterium acnes comparable to its major component-citral. An in vitro toxicological study based on the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cytotoxicity assay was performed. In vitro cytotoxicity testing indicated that both lemon myrtle oil and citral had a very toxic effect against human cell lines: HepG2 (a hepatocarcinoma-derived cell line); F1-73 (a fibroblast cell line derived from normal skin) and primary cell cultures of human skin fibroblasts. Cytotoxicity IC50 (50% inhibitory concentration) values ranged from 0.008 to 0.014% (w/v) at 4 h to 0.003-0.012% (w/v) at 24 h of exposure. The no-observed-adverse-effect level (NOAEL) for lemon myrtle oil was calculated as 0.5 mg/l at 24 h exposure and the RfD (reference dose) was determined as 0.01 mg/l. A product containing 1% lemon myrtle oil was found to be low in toxicity and could potentially be used in the formulation of topical antimicrobial products.

Topics: Carcinoma, Hepatocellular; Fibroblasts; Humans; Lethal Dose 50; Liver Neoplasms; Microbial Sensitivity Tests; Myrtaceae; No-Observed-Adverse-Effect Level; Oils, Volatile; Plant Extracts; Reference Values; Toxicity Tests; Tumor Cells, Cultured

Hepatocellular carcinoma (HCC) etiology and incidence in Madagascar are not well established. The work presented here is the first documented study on HCC in Madagascar. The study was undertaken at the Centre Hospitalier de Soavinandriana, Antananarivo, from October 1995 to October 1996. Hepatocellular carcinoma was reported in 19 out of 22 patients with liver tumor included in the study. In 6 cases, patients developed post alcoholic cirrhosis HCC. Hepatitis B virus markers were detected in 48% of cases (13/19). The HBs Ag was detected in 42% of cases (8/19) in association with HBe Ag in 16% of cases (3/19), and hepatitis C virus antibodies in 11% of cases (2/18). In 3 cases, the etiology remained unknown. Hepatocellular carcinoma appeared the most frequent liver cancer, mainly due to post-hepatitis B cirrhosis. The introduction of hepatitis B vaccine in EPI (Expanded Program of Immunization) is recommended in order to reduce the percentage of hepatitis B virus carriers in the malagasy population and furthermore the incidence of HCC.

Topics: Adolescent; Adult; Age Distribution; Aged; Biopsy, Needle; Carcinoma, Hepatocellular; Child; Child, Preschool; Female; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis C Antibodies; Humans; Liver Neoplasms; Madagascar; Male; Middle Aged; Seroepidemiologic Studies; Sex Distribution

Available data on cancer rates in Madagascar are given. Cervical cancer is the most common, accounting for 28% of diagnosed tumours and 47% of genital tumours in women. It occurs most often in women of about 40 years of age. Penile cancer represents 5.2% of male tumours but occurs at different rates in various ethnic groups. Kaposi's sarcoma is rare in Madagascar. Equally hepatocellular carcinoma occurs at a low incidence in this country and is found most frequently in males over the age of 40 years. Cancer control programmes and the problems they encounter are also discussed.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Madagascar; Male; Middle Aged; Neoplasms; Penile Neoplasms; Sarcoma, Kaposi; Uterine Cervical Neoplasms

Topics: Adolescent; Adult; Age Factors; Aged; Breast Neoplasms; Child; Child, Preschool; Digestive System Neoplasms; Ethnicity; Eye Neoplasms; Female; Humans; Hydatidiform Mole; Hydatidiform Mole, Invasive; Infant; Infant, Newborn; Liver Neoplasms; Madagascar; Male; Middle Aged; Neoplasms; Pregnancy; Retinoblastoma; Sex Factors; Thyroid Neoplasms; Uterine Cervical Neoplasms

Topics: Asian People; Humans; Liver Neoplasms; Madagascar; Neoplasms