Displaying publications 1 - 20 of 29 in total

Abstract:
Sort:
  1. Abdul Rahman Sazli F, Jubri Z, Abdul Rahman M, Karsani SA, Md Top AG, Wan Ngah WZ
    PMID: 25886747 DOI: 10.1186/s12906-015-0590-y
    To determine the antiproliferative effect of gamma-tocotrienol (GTT) treatment on differential protein expression in HepG2 cells.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  2. Abdull Razis AF, Noor NM
    Asian Pac J Cancer Prev, 2013;14(7):4235-8.
    PMID: 23991982
    Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 μM) for 24 hours. Glucoraphanin at higher concentration (25 μM) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 μM. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen- metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  3. Anasamy T, Chee CF, Kiew LV, Chung LY
    Eur J Pharm Sci, 2020 Jan 15;142:105140.
    PMID: 31704345 DOI: 10.1016/j.ejps.2019.105140
    This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ± 0.8 nm) and PLGA-C9 (163.2 ± 1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  4. Azhar NA, Ghozali SZ, Abu Bakar SA, Lim V, Ahmad NH
    Toxicol In Vitro, 2020 Sep;67:104910.
    PMID: 32526345 DOI: 10.1016/j.tiv.2020.104910
    Application of silver nanoparticles serves as a new approach in cancer treatment due to its unique features. Biosynthesis of silver nanoparticles using plant is advantageous since they are easily accessible, nontoxic and produce quicker reaction compared to other methods. To evaluate the cytotoxicity, mechanism of cell death and DNA damage of biosynthesized Catharanthus roseus-silver nanoparticles on human liver cancer (HepG2) cells. The antiproliferative activity of Catharanthus roseus‑silver nanoparticles was measured using MTT assay. The cytotoxic effects were further evaluated by measuring nitric oxide and reactive oxygen species (ROS). The mechanism of cell death was determined by annexin-FITC/propidium iodide, mitochondrial membrane potential (MMP) and cell cycle assays. The assessment of DNA damage was evaluated using Comet assay method. The uptake of the nanoparticles were evaluated by Transmission Electron Microscopy (TEM). Catharanthus roseus‑silver nanoparticles has inhibited the proliferation of HepG2 cells in a time-dependent manner with a median IC50 value of 3.871 ± 0.18 μg/mL. The concentration of nitrite and ROS were significantly higher than control. The cell death was due to apoptosis associated with MMP loss, cell cycle arrest, and extensive DNA damage. TEM analysis indicated the presence of free nanoparticles and endosomes containing the nanoparticles. The findings show that Catharanthus roseus‑silver nanoparticles have produced cytotoxic effects on HepG2 cells and thus may have a potential to be used as an anticancer treatment, particularly for hepatocellular carcinoma.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  5. Bhullar M, Bhullar A, Arachchi NJ
    Ann Acad Med Singap, 2016 Oct;45(10):479-480.
    PMID: 27832225
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  6. Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.
    Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
    PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17
    OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.

    METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.

    RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.

    CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
    .

    Matched MeSH terms: Liver Neoplasms/drug therapy
  7. Chow PK, Poon DY, Khin MW, Singh H, Han HS, Goh AS, et al.
    PLoS One, 2014;9(3):e90909.
    PMID: 24614178 DOI: 10.1371/journal.pone.0090909
    The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  8. Ebadi M, Bullo S, Buskara K, Hussein MZ, Fakurazi S, Pastorin G
    Sci Rep, 2020 Dec 09;10(1):21521.
    PMID: 33298980 DOI: 10.1038/s41598-020-76504-5
    The use of nanocarriers composed of polyethylene glycol- and polyvinyl alcohol-coated vesicles encapsulating active molecules in place of conventional chemotherapy drugs can reduce many of the chemotherapy-associated challenges because of the increased drug concentration at the diseased area in the body. The present study investigated the structure and magnetic properties of iron oxide nanoparticles in the presence of polyvinyl alcohol and polyethylene glycol as the basic surface coating agents. We used superparamagnetic iron oxide nanoparticles (FNPs) as the core and studied their effectiveness when two polymers, namely polyvinyl alcohol (PVA) and polyethylene glycol (PEG), were used as the coating agents together with magnesium-aluminum-layered double hydroxide (MLDH) as the nanocarrier. In addition, the anticancer drug sorafenib (SO), was loaded on MLDH and coated onto the surface of the nanoparticles, to best exploit this nano-drug delivery system for biomedical applications. Samples were prepared by the co-precipitation method, and the resulting formation of the nanoparticles was confirmed by X-ray, FTIR, TEM, SEM, DLS, HPLC, UV-Vis, TGA and VSM. The X-ray diffraction results indicated that all the as-synthesized samples contained highly crystalline and pure Fe3O4. Transmission electron microscopy analysis showed that the shape of FPEGSO-MLDH nanoparticles was generally spherical, with a mean diameter of 17 nm, compared to 19 nm for FPVASO-MLDH. Fourier transform infrared spectroscopy confirmed the presence of nanocarriers with polymer-coating on the surface of iron oxide nanoparticles and the existence of loaded active drug consisting of sorafenib. Thermogravimetric analyses demonstrated the thermal stability of the nanoparticles, which displayed enhanced anticancer effect after coating. Vibrating sample magnetometer (VSM) curves of both produced samples showed superparamagnetic behavior with the high saturation magnetization of 57 emu/g for FPEGSO-MLDH and 49 emu/g for FPVASO-MLDH. The scanning electron microscopy (SEM) images showed a narrow size distribution of both final samples. The SO drug loading and the release behavior from FPEGSO-MLDH and FPVASO-MLDH were assessed by ultraviolet-visible spectroscopy. This evaluation showed around 85% drug release within 72 h, while 74% of sorafenib was released in phosphate buffer solution at pH 4.8. The release profiles of sorafenib from the two designed samples were found to be sustained according to pseudo-second-order kinetics. The cytotoxicity studies confirmed the anti-cancer activity of the coated nanoparticles loaded with SO against liver cancer cells, HepG2. Conversely, the drug delivery system was less toxic than the pure drug towards fibroblast-type 3T3 cells.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  9. Hafidh RR, Hussein SZ, MalAllah MQ, Abdulamir AS, Abu Bakar F
    Curr Cancer Drug Targets, 2018;18(8):807-815.
    PMID: 29141549 DOI: 10.2174/1568009617666171114144236
    BACKGROUND: Citrus bioactive compounds, as active anticancer agents, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted.

    OBJECTIVES: The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene.

    METHODS: The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of the pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. Highthroughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development.

    RESULTS: In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene- driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from the most to the least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins.

    CONCLUSION: The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines.

    Matched MeSH terms: Liver Neoplasms/drug therapy*
  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: Liver Neoplasms/drug therapy*
  11. Huang D, Guo W, Gao J, Chen J, Olatunji JO
    Molecules, 2015;20(9):17405-28.
    PMID: 26393569 DOI: 10.3390/molecules200917405
    Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⁺ T cells and decreased the number of IL-4⁺ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  12. Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Zainal Z, Hakim MN
    Int J Nanomedicine, 2011;6:3099-111.
    PMID: 22163163 DOI: 10.2147/IJN.S24510
    A new simple preparation method for a hippurate-intercalated zinc-layered hydroxide (ZLH) nanohybrid has been established, which does not need an anion-exchange procedure to intercalate the hippurate anion into ZLH interlayers.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  13. Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A
    BMC Complement Altern Med, 2014 Jan 20;14:32.
    PMID: 24444147 DOI: 10.1186/1472-6882-14-32
    BACKGROUND: This paper is to investigate the effects of Centella asiatica on HepG2 (human hepatocellular liver carcinoma cell line). Centella asiatica is native to the Southeast Asia that is used as a traditional medicine. This study aims to determine the chemopreventive effects of the Centella asiatica juice on human HepG2 cell line.

    METHODS: Different methods including flow cytometry, comet assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to show the effects of juice exposure on the level of DNA damage and the reduction of cancerous cells. MTT assay is a colorimetric method applied to measure the toxic effects of juice on cells.

    RESULTS: The Centella asiatica juice was not toxic to normal cells. It showed cytotoxic effects on tumor cells in a dose dependent manner. Apoptosis in cells was started after being exposed for 72 hr of dose dependent. It was found that the higher percentage of apoptotic cell death and DNA damage was at the concentration above 0.1%. In addition, the juice exposure caused the reduction of c-myc gene expression and the enhancement of c-fos and c-erbB2 gene expressions in tumor cells.

    CONCLUSIONS: It was concluded that the Centella asiatica juice reduced liver tumor cells. Thus, it has the potential to be used as a chemopreventive agent to prevent and treat liver cancer.

    Matched MeSH terms: Liver Neoplasms/drug therapy*
  14. Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z
    Asian Pac J Cancer Prev, 2015;16(14):6047-53.
    PMID: 26320494
    BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.

    OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.

    MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.

    RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.

    CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

    Matched MeSH terms: Liver Neoplasms/drug therapy
  15. Jaganathan A, Murugan K, Panneerselvam C, Madhiyazhagan P, Dinesh D, Vadivalagan C, et al.
    Parasitol Int, 2016 Jun;65(3):276-84.
    PMID: 26873539 DOI: 10.1016/j.parint.2016.02.003
    The development of parasites and pathogens resistant to synthetic drugs highlighted the needing of novel, eco-friendly and effective control approaches. Recently, metal nanoparticles have been proposed as highly effective tools towards cancer cells and Plasmodium parasites. In this study, we synthesized silver nanoparticles (EW-AgNP) using Eudrilus eugeniae earthworms as reducing and stabilizing agents. EW-AgNP showed plasmon resonance reduction in UV-vis spectrophotometry, the functional groups involved in the reduction were studied by FTIR spectroscopy, while particle size and shape was analyzed by FESEM. The effect of EW-AgNP on in vitro HepG2 cell proliferation was measured using MTT assays. Apoptosis assessed by flow cytometry showed diminished endurance of HepG2 cells and cytotoxicity in a dose-dependent manner. EW-AgNP were toxic to Anopheles stephensi larvae and pupae, LC(50) were 4.8 ppm (I), 5.8 ppm (II), 6.9 ppm (III), 8.5 ppm (IV), and 15.5 ppm (pupae). The antiplasmodial activity of EW-AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. EW-AgNP IC(50) were 49.3 μg/ml (CQ-s) and 55.5 μg/ml (CQ-r), while chloroquine IC(50) were 81.5 μg/ml (CQ-s) and 86.5 μg/ml (CQ-r). EW-AgNP showed a valuable antibiotic potential against important pathogenic bacteria and fungi. Concerning non-target effects of EW-AgNP against mosquito natural enemies, the predation efficiency of the mosquitofish Gambusia affinis towards the II and II instar larvae of A. stephensi was 68.50% (II) and 47.00% (III), respectively. In EW-AgNP-contaminated environments, predation was boosted to 89.25% (II) and 70.75% (III), respectively. Overall, this research highlighted the EW-AgNP potential against hepatocellular carcinoma, Plasmodium parasites and mosquito vectors, with little detrimental effects on mosquito natural enemies.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  16. Joishy SK, Bennett JM, Balasegaram M, MacIntyre JM, Falkson G, Moertel C, et al.
    Cancer, 1982 Sep 15;50(6):1065-9.
    PMID: 6286085
    Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  17. Kadir FA, Kassim NM, Abdulla MA, Yehye WA
    PMID: 24305067 DOI: 10.1186/1472-6882-13-343
    Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effects, biological and biochemical mechanisms based on the structural formula of the substance was efficiently used in this study to reveal new multitalented actions for Vitex negundo (VN) constituents.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  18. Katiman D, Manikam J, Goh KL, Abdullah BJ, Mahadeva S
    J Gastrointest Cancer, 2012 Sep;43 Suppl 1:S187-90.
    PMID: 22692948 DOI: 10.1007/s12029-012-9373-6
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  19. Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  20. 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: Liver Neoplasms/drug therapy*
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links