Displaying publications 21 - 39 of 39 in total

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  1. Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF
    Nutrients, 2018 Jun 04;10(6).
    PMID: 29866995 DOI: 10.3390/nu10060718
    Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  2. Cheah PL, Looi LM, Lin HP, Yap SF
    Pathology, 1991 Jan;23(1):66-8.
    PMID: 1648195
    A case of primary hepatocellular carcinoma (PHC) developing in a 10 year old boy who contracted Hepatitis B virus (HBV) infection in the course of maintenance phase chemotherapy for acute lymphoblastic leukemia was seen at University Hospital, Kuala Lumpur. This case is of interest in that it (1) supports an etiological relationship between HBV infection and PHC, (2) manifested a distinctly short malignant transformation time, and (3) draws attention to the possible contributory role of chemotherapy in increasing the risk of developing PHC.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  3. Ban KC, Singh H, Krishnan R, Seow HF
    Cancer Lett, 2003 Sep 25;199(2):201-8.
    PMID: 12969793
    The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p=0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p<0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  4. Isa NM, Bong JJ, Ghani FA, Rose IM, Husain S, Azrif M
    Diagn Cytopathol, 2012 Nov;40(11):1010-4.
    PMID: 21563319 DOI: 10.1002/dc.21706
    Cutaneous metastasis of hepatocellular carcinoma (HCC) is very rare, accounting for less than 0.8% of all known cutaneous metastases and occurring in 2.7-3.4% of HCCs. With less than 50 such cases reported worldwide, most of which were diagnosed histologically on excised lesions, it can only be expected that diagnosis made on cytological features alone would be challenging. We report a case of cutaneous metastasis of HCC diagnosed based on cytological features and confirmed by Hep Par 1 immunopositivity of the cell block material. An 81-year-old man, who was known to have unresectable HCC, presented with a 1-month history of painless, left nasal alae mass. The mass measured 1.5 cm in diameter, and was multilobulated with a central necrosis. Fine needle aspiration of the mass was done. Smears were cellular, comprising of malignant cells in loose clusters and aggregates as well as singly dispersed. The malignant cells displayed moderate nuclear pleomorphism, occasional prominent nucleoli, and intranuclear pseudoinclusion. Cell block material demonstrated the trabeculae pattern of the malignant cells and Hep Par 1 immunopositivity. The final diagnosis of a metastatic cutaneous HCC was made. In conclusion, cutaneous HCC metastasis is rare and should be considered in the differential diagnosis in patients with a history of HCC presenting with suspicious skin lesion. In the right clinical setting, a confident diagnosis can be made in such cases by using the fine needle aspiration technique aided with immunopositivity for Hep Par 1 antibody of the aspirated material.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  5. Rahman FA, Naidu J, Ngiu CS, Yaakob Y, Mohamed Z, Othman H, et al.
    Asian Pac J Cancer Prev, 2016;17(8):4037-41.
    PMID: 27644658
    BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer that is frequently diagnosed at an advanced stage. Transarterial chemoembolisation (TACE) is an effective palliative treatment for patients who are not eligible for curative treatment. The two main methods for performing TACE are conventional (c-TACE) or with drug eluting beads (DEB-TACE). We sought to compare survival rates and tumour response between patients undergoing c-TACE and DEB-TACE at our centre.

    MATERIALS AND METHODS: A retrospective cohort study of patients undergoing either treatment was carried out from January 2009 to December 2014. Tumour response to the procedures was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Kaplan-Meier analysis was used to assess and compare the overall survival in the two groups.

    RESULTS: A total of 79 patients were analysed (34 had c-TACE, 45 had DEB-TACE) with a median follow-up of 11.8 months. A total of 20 patients in the c-TACE group (80%) and 12 patients in the DEB-TACE group (44%) died during the follow up period. The median survival durations in the c-TACE and DEB-TACE groups were 4.9 ± 3.2 months and 8.3 ± 2.0 months respectively (p=0.008). There was no statistically significant difference noted among the two groups with respect to mRECIST criteria.

    CONCLUSIONS: DEB-TACE demonstrated a significant improvement in overall survival rates for patients with unresectable HCC when compared to c-TACE. It is a safe and promising approach and should potentially be considered as a standard of care in the management of unresectable HCC.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  6. Dai X, Wang L, Deivasigamni A, Looi CY, Karthikeyan C, Trivedi P, et al.
    Oncotarget, 2017 Feb 21;8(8):12831-12842.
    PMID: 28086233 DOI: 10.18632/oncotarget.14606
    A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  7. Waziri PM, Abdullah R, Rosli R, Omar AR, Abdul AB, Kassim NK, et al.
    Asian Pac J Cancer Prev, 2018 Apr 25;19(4):917-922.
    PMID: 29693341
    Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
    plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
    The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
    death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
    protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
    analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
    effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
    activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
    cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
    apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
    factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
    carcinoma cells.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  8. Sawai S, Mohktar MS, Safwani WKZW, Ramasamy TS
    Anticancer Agents Med Chem, 2018;18(9):1258-1266.
    PMID: 29521251 DOI: 10.2174/1871520618666180307143229
    BACKGROUND: Konjac Glucomannan (KGM) is a water-soluble dietary fibre extracted from Amorphophallus konjac K. Koch (Araceae). Konjac fibre has been clinically proven as an effective antioxidant agent in weight control but its traditionally known tumour suppression property remains to be explored.

    OBJECTIVE: The main objective of this study is to determine the potential anti-proliferative effect of KGM on cancer and normal human liver cell lines, HepG2 and WRL68, respectively.

    METHOD: HepG2 and WRL68 cells were treated with KGM, D-mannose, KGM-D-mannose and 5-fluorouracil. The morphological changes in those treated cells were observed. Cytotoxic effect of the treatments on cell viability and proliferation, and apoptosis genes expression were assessed by cytotoxicity assay, flow cytometry and RT-PCR analyses.

    RESULTS: The results show that KGM treatment resulted in reduced viability of HepG2 cells significantly, in line with the apoptosis-like morphological changes. Up-regulation of BAX and down-regulation of BCL2 genes as reflected by high Bax to Bcl 2 ratio suggests that the inhibitory effect of KGM on HepG2 cells most likely via Bcl2/Bax protein pathway. Despite the effectiveness of standard drug 5-FU in suppressing the viability and proliferation of HepG2 cells, it however, exhibited no selective inhibition of cancer cells as compared to KGM.

    CONCLUSION: Current findings suggested that KGM is a potential anti-cancer compound/drug entity, which could be an alternative preventive agent against liver cancer.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  9. Qi Qi C, Ajit Singh V
    BMJ Case Rep, 2012;2012.
    PMID: 22892228 DOI: 10.1136/bcr.01.2012.5518
    The authors present an interesting case under our follow-up who has had five different forms of tumours with different pathologies throughout his lifetime. He started off with hepatoma, followed by pleomorphic sarcoma of the thigh, adenocarcinoma of the prostate, meningioma and finally schwanoma. He is still alive to this date.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  10. Handayani T, Sakinah S, Nallappan M, Pihie AH
    Anticancer Res, 2007 Mar-Apr;27(2):965-71.
    PMID: 17465228
    Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  11. Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.
    Cancer Epidemiol, 2016 Feb;40:179-87.
    PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002
    INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

    METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

    RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).

    CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  12. Lopez JB, Balasegaram M, Timor J, Thambyrajah V
    Malays J Pathol, 1997 Jun;19(1):53-8.
    PMID: 10879242
    Although alpha-fetoprotein (AFP) is regarded as the reference marker for hepatocellular carcinoma (HCC), it sometimes produces false results. The objective of this study was to see if some of the readily available laboratory markers could complement AFP to improve the laboratory diagnosis of HCC. The markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19-9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and AFP, 97.4%. The specificities of the other markers were less impressive: CEA, 77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M, 39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are based on the consideration of sensitivity and specificity together, were as follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%; CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is proposed that CA 125 be combined with AFP for HCC screening because of their excellent sensitivity and specificity, respectively: a negative result for both, or even just CA 125 alone, would indicate that the disease is unlikely while a positive AFP (which would likely occur with a positive CA 125) would make its presence highly probable. A positive CA 125 and negative AFP would be equivocal for HCC. Other markers in combination with AFP are less useful.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  13. Chuon C, Takahashi K, Matsuo J, Katayama K, Yamamoto C, Ko K, et al.
    Sci Rep, 2019 08 21;9(1):12186.
    PMID: 31434918 DOI: 10.1038/s41598-019-48304-z
    Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P 
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  14. Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, et al.
    Clin Cancer Res, 2018 01 01;24(1):73-83.
    PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433
    Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology*
  15. Chan TT, Chan WK, Wong GL, Chan AW, Nik Mustapha NR, Chan SL, et al.
    Am J Gastroenterol, 2020 06;115(6):867-875.
    PMID: 32149781 DOI: 10.14309/ajg.0000000000000588
    OBJECTIVES: Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD).

    METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection.

    RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity.

    DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  16. Tajul Arifin K, Sulaiman S, Md Saad S, Ahmad Damanhuri H, Wan Ngah WZ, Mohd Yusof YA
    BMC Cancer, 2017 12 21;17(1):879.
    PMID: 29268718 DOI: 10.1186/s12885-017-3883-3
    BACKGROUND: Chlorella vulgaris (ChV), a unicellular green algae has been reported to have anticancer and antioxidant effects. The aim of this study was to determine the chemopreventive effect of ChV on liver cancer induced rats by determining the level and expression of several liver tumour markers.

    METHODS: Male Wistar rats (200-250 g) were divided into 4 groups according to the diet given: control group (normal diet), ChV group with three different doses (50, 150 and 300 mg/kg body weight), liver cancer- induced group (choline deficient diet + 0.1% ethionine in drinking water or CDE group), and the treatment group (CDE group treated with three different doses of ChV). Rats were killed at 0, 4, 8 and 12 weeks of experiment and blood and tissue samples were taken from all groups for the determination of tumour markers expression alpha-fetoprotein (AFP), transforming growth factor-β (TGF-β), M2-pyruvate kinase (M2-PK) and specific antigen for oval cells (OV-6).

    RESULTS: Serum level of TGF-β increased significantly (p < 0.05) in CDE rats. However, ChV at all doses managed to decrease (p < 0.05) its levels to control values. Expressions of liver tumour markers AFP, TGF-β, M2-PK and OV-6 were significantly higher (p < 0.05) in tissues of CDE rats when compared to control showing an increased number of cancer cells during hepatocarcinogenesis. ChV at all doses reduced their expressions significantly (p < 0.05).

    CONCLUSIONS: Chlorella vulgaris has chemopreventive effect by downregulating the expression of tumour markers M2-PK, OV-6, AFP and TGF-β, in HCC-induced rats.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  17. Mohamed GA, Al-Abd AM, El-Halawany AM, Abdallah HM, Ibrahim SRM
    J Ethnopharmacol, 2017 Feb 23;198:302-312.
    PMID: 28108382 DOI: 10.1016/j.jep.2017.01.030
    ETHNOPHARMACOLOGICAL RELEVANCE: Cancer has proceeded to surpass one of the most chronic illnesses to be the major cause of mortality in both the developing and developed world. Garcinia mangostana L. (mangosteen, family Guttiferae) known as the queen of fruits, is one of the most popular tropical fruits. It is cultivated in Southeast Asian countries: Malaysia, Indonesia, Sri Lanka, Burma, Thailand, and Philippines. Traditionally, numerous parts of G. mangostana have been utilized to treat various ailments such as abdominal pain, haemorrhoids, food allergies, arthritis, leucorrhoea, gonorrhea, diarrhea, dysentery, wound infection, suppuration, and chronic ulcer.

    AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.

    MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.

    RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.

    CONCLUSION: Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.

    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  18. Buskaran K, Hussein MZ, Moklas MAM, Masarudin MJ, Fakurazi S
    Int J Mol Sci, 2021 May 28;22(11).
    PMID: 34071389 DOI: 10.3390/ijms22115786
    Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75-90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide-polyethylene glycol (GOP)-PCA/CA-FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP-PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
  19. Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S
    Chem Biol Interact, 2010 Aug 05;186(3):295-305.
    PMID: 20452335 DOI: 10.1016/j.cbi.2010.04.029
    Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.
    Matched MeSH terms: Carcinoma, Hepatocellular/pathology
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