Displaying publications 1 - 20 of 99 in total

Abstract:
Sort:
  1. Dahham SS, Tabana Y, Asif M, Ahmed M, Babu D, Hassan LE, et al.
    Int J Mol Sci, 2021 Sep 29;22(19).
    PMID: 34638895 DOI: 10.3390/ijms221910550
    Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
    Matched MeSH terms: HCT116 Cells
  2. Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB
    J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
    PMID: 24398912 DOI: 10.1007/s10856-013-5132-x
    Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
    Matched MeSH terms: HCT116 Cells
  3. Yu F, Bracken CP, Pillman KA, Lawrence DM, Goodall GJ, Callen DF, et al.
    PLoS One, 2015;10(6):e0129190.
    PMID: 26061048 DOI: 10.1371/journal.pone.0129190
    p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs) are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.
    Matched MeSH terms: HCT116 Cells
  4. Aisha AF, Abu-Salah KM, Ismail Z, Majid AM
    Molecules, 2012;17(3):2939-54.
    PMID: 22402764 DOI: 10.3390/molecules17032939
    Despite the progress in colon cancer treatment, relapse is still a major obstacle. Hence, new drugs or drug combinations are required in the battle against colon cancer. α-Mangostin and betulinic acid (BA) are cytotoxic compounds that work by inducing the mitochondrial apoptosis pathway, and cisplatin is one of the most potent broad spectrum anti-tumor agents. This study aims to investigate the enhancement of BA cytotoxicity by α-mangostin, and the cytoprotection effect of α-mangostin and BA on cisplatin-induced cytotoxicity on HCT 116 human colorectal carcinoma cells. Cytotoxicity was investigated by the XTT cell proliferation test, and the apoptotic effects were investigated on early and late markers including caspases-3/7, mitochondrial membrane potential, cytoplasmic shrinkage, and chromatin condensation. The effect of α-mangostin on four signalling pathways was also investigated by the luciferase assay. α-Mangostin and BA were more cytotoxic to the colon cancer cells than to the normal colonic cells, and both compounds showed a cytoprotective effect against cisplatin-induced cytotoxicity. On the other hand, α-mangostin enhanced the cytotoxic and apoptotic effects of BA. Combination therapy hits multiple targets, which may improve the overall response to the treatment, and may reduce the likelihood of developing drug resistance by the tumor cells. Therefore, α-mangostin and BA may provide a novel combination for the treatment of colorectal carcinoma. The cytoprotective effect of the compounds against cisplatin-induced cytotoxicity may find applications as chemopreventive agents against carcinogens, irradiation and oxidative stress, or to neutralize cisplatin side effects.
    Matched MeSH terms: HCT116 Cells
  5. Mohebali N, Pandurangan AK, Mustafa MR, Anandasadagopan SK, Alagumuthu T
    J Biochem Mol Toxicol, 2020 Dec;34(12):e22587.
    PMID: 32726518 DOI: 10.1002/jbt.22587
    Colorectal cancer is one of the most leading death-causing cancers in the world. Vernodalin, a cytotoxic sesquiterpene, has been reported to possess anticancer properties against human breast cancer cells. We aimed to examine the anticancer mechanism of vernodalin on human colon cancer cells. Vernodalin was used on human colon cancer cells, HT-29 and HCT116. The cytotoxicity of vernodalin on human colon cancer cells was determined through in vitro 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Small interfering RNA was used to analyze the cascade activation of mitogen-activated protein kinase (MAPK) pathway, c-Jun N-terminal kinase (JNK) in HT-29, and HCT116 cells against vernodalin treatment. The protein expressions of caspase 3, Bcl-2, and Bax were examined through Western blot analysis. Immunoblot analysis on the JNK, ERK, and p38 MAPK pathways showed increased activation due to vernodalin treatment. It was proven from the JNK and p38 inhibition test that both pathways are significantly activated by vernodalin to induce apoptosis. Our results, collectively, showed the apoptosis-induced anticancer mechanism of vernodalin on human colon cancer cells that was mediated through the activation of JNK pathway and apoptotic regulator proteins. These results suggest that vernodalin could be developed as a potent chemotherapeutic agent for human colorectal cancer treatment.
    Matched MeSH terms: HCT116 Cells
  6. Soh JE, Abu N, Sagap I, Mazlan L, Yahaya A, Mustangin M, et al.
    Immunotherapy, 2019 10;11(14):1205-1219.
    PMID: 31478431 DOI: 10.2217/imt-2019-0073
    Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.
    Matched MeSH terms: HCT116 Cells
  7. Lau BF, Abdullah N, Aminudin N, Lee HB, Yap KC, Sabaratnam V
    PLoS One, 2014;9(7):e102509.
    PMID: 25054862 DOI: 10.1371/journal.pone.0102509
    Previous studies on the nutritional and nutraceutical properties of Lignosus rhinocerotis focused mainly on the sclerotium; however, the supply of wild sclerotium is limited. In this investigation, the antioxidant capacity and cytotoxic effect of L. rhinocerotis cultured under different conditions of liquid fermentation (shaken and static) were compared to the sclerotium produced by solid-substrate fermentation. Aqueous methanol extracts of the mycelium (LR-MH, LR-MT) and culture broth (LR-BH, LR-BT) demonstrated either higher or comparable antioxidant capacities to the sclerotium extract (LR-SC) based on their radical scavenging abilities, reducing properties, metal chelating activities, and inhibitory effects on lipid peroxidation. All extracts exerted low cytotoxicity (IC50>200 µg/ml, 72 h) against selected mammalian cell lines. Several low-molecular-weight compounds, including sugars, fatty acids, methyl esters, sterols, amides, amino acids, phenolics, and triterpenoids, were identified using GC-MS and UHPLC-ESI-MS/MS. The presence of proteins (<40 kDa) in the extracts was confirmed by SDS-PAGE and SELDI-TOF-MS. Principal component analysis revealed that the chemical profiles of the mycelial extracts under shaken and static conditions were distinct from those of the sclerotium. Results from bioactivity evaluation and chemical profiling showed that L. rhinocerotis from liquid fermentation merits consideration as an alternative source of functional ingredients and potential substitute for the sclerotium.
    Matched MeSH terms: HCT116 Cells
  8. Yusefi M, Shameli K, Jahangirian H, Teow SY, Umakoshi H, Saleh B, et al.
    Int J Nanomedicine, 2020;15:5417-5432.
    PMID: 32801697 DOI: 10.2147/IJN.S250047
    INTRODUCTION: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy.

    MATERIALS AND METHODS: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment.

    RESULTS: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively.

    DISCUSSION: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.

    Matched MeSH terms: HCT116 Cells
  9. Arfan M, Siddiqui SZ, Abbasi MA, Rehman A, Shah SAA, Ashraf M, et al.
    Pak J Pharm Sci, 2018 Nov;31(6 (Supplementary):2697-2708.
    PMID: 30587482
    The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide (1) was cyclized with phenyl isothiocyanate (2) via 2-(4-methoxybenzoyl)-N-phenylhydrazinecarbothioamide (3); an intermediate to 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-thiol (4). The electrophiles; alkyl halides 5(a-g) were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols 6(a-g). Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-(n-heptylthio)-5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole; 6g against AChE (IC50; 38.35±0.62μM) and BChE (IC50; 147.75±0.67μM) enzymes. Eserine (IC50; 0.04±0.01μM) was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability (6g) at 25μM and with 2.41% cell viability at 50μMamong library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics.
    Matched MeSH terms: HCT116 Cells
  10. Ahmad N, Anouar EH, Tajuddin AM, Ramasamy K, Yamin BM, Bahron H
    PLoS One, 2020;15(4):e0231147.
    PMID: 32287324 DOI: 10.1371/journal.pone.0231147
    This paper reports the synthesis, characterization, anticancer screening and quantum chemical calculation of a tetradentate Schiff base 2,2'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis- (azanylylidene))bis(methanylylidene))bis(4-fluorophenol) (L2F) and its Pd (II) complex (PdL2F). The compounds were characterized via UV-Visible, NMR, IR spectroscopy and single crystal x-ray diffraction. Density Functional Theory (DFT) and time-dependent DFT calculations in gas and solvent phases were carried out using B3LYP, B3P86, CAM-B3LYP and PBE0 hybrid functionals combined with LanL2DZ basis set. Complexation of L2F to form PdL2F was observed to cause a bathochromic shift of the maximum absorption bands of n-π* from 327 to 410 nm; an upfield shift for δ (HC = N) from 8.30 to 7.96 ppm and a decreased wavenumber for ν(C = N) from 1637 to 1616 cm-1. Overall, the UV-Vis, NMR and IR spectral data are relatively well reproduced through DFT and TD-DFT methods. L2F and PdL2F showed IC50 of 90.00 and 4.10 μg/mL, respectively, against human colorectal carcinoma (HCT116) cell lines, signifying increased anticancer activity upon complexation with Pd (II).
    Matched MeSH terms: HCT116 Cells
  11. Kashyap S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Om H, et al.
    Chem Cent J, 2018 Nov 20;12(1):117.
    PMID: 30460466 DOI: 10.1186/s13065-018-0487-1
    BACKGROUND: The transition metal complexes formed from Schiff base is regarded as leading molecules in medicinal chemistry. Because of the preparative availability and diversity in the structure of central group, the transition metals are important in coordination chemistry. In the present work, we have designed and prepared Schiff base and its metal complexes (MC1-MC4) and screened them for antimicrobial, anticancer and corrosion inhibitory properties.

    METHODOLOGY: The synthesized metal complexes were characterized by physicochemical and spectral investigation (UV, IR, 1H and 13C-NMR) and were further evaluated for their antimicrobial (tube dilution) and anticancer (SRB assay) activities. In addition, the corrosion inhibition potential was determined by electrochemical impedance spectroscopy (EIS) technique.

    RESULTS AND DISCUSSION: Antimicrobial screening results found complexes (MC1-MC4) to exhibit less antibacterial activity against the tested bacterial species compared to ofloxacin while the complex MC1 exhibited greater antifungal activity than the fluconazole. The anticancer activity results found the synthesized Schiff base and its metal complexes to elicit poor cytotoxic activity than the standard drug (5-fluorouracil) against HCT116 cancer cell line. Metal complex MC2 showed more corrosion inhibition efficiency with high Rct values and low Cdl values.

    CONCLUSION: From the results, we can conclude that complexes MC1 and MC2 may be used as potent antimicrobial and anticorrosion agents, respectively.

    Matched MeSH terms: HCT116 Cells
  12. Atif M, Bhatti HN, Haque RA, Iqbal MA, Ahamed Khadeer MB, Majid AMSA
    Appl Biochem Biotechnol, 2020 Jul;191(3):1171-1189.
    PMID: 32002729 DOI: 10.1007/s12010-019-03186-9
    Synthesis and anticancer studies of three symmetrically and non-symmetrically substituted silver(I)-N-Heterocyclic carbene complexes of type [(NHC)2-Ag]PF6 (7-9) and their respective (ligands) benzimidazolium salts (4-6) are described herein. Compound 5 and Ag-NHC-complex 7 were characterized by the single crystal X-ray diffraction technique. Structural studies for 7 showed that the silver(I) center has linear C-Ag-C coordination geometry (180.00(10)o). Other azolium and Ag-NHC analogues were confirmed by H1 and C13-NMR spectroscopy. The synthesized analogues were biologically characterized for in vitro anticancer activity against three cancer cell lines including human colorectal cancer (HCT 116), breast cancer (MCF-7), and erythromyeloblastoid leukemia (K-562) cell lines and in terms of in vivo acute oral toxicity (IAOT) in view of agility and body weight of female rats. In vitro anticancer activity showed the values of IC50 in range 0.31-17.9 μM in case of K-562 and HCT-116 cancer cell lines and 15.1-35.2 μM in case of MCF-7 while taking commercially known anticancer agents 5-fluorouracil, tamoxifen, and betulinic acid which have IC50 values 5.2, 5.5, and 17.0 μM, respectively. In vivo study revealed vigor and agility of all test animals which explores the biocompatibility and non-toxicity of the test analogues.
    Matched MeSH terms: HCT116 Cells
  13. Mishra A, Tahlan S, Ramasamy K, Lim SM, Shah SAA, Narasimhan B
    Mini Rev Med Chem, 2020;20(13):1311-1317.
    PMID: 32368977 DOI: 10.2174/1389557520666200505124125
    BACKGROUND: Being derived from primary amine and aromatic aldehyde, Schiff base and their complexes have an imperative role in the improvement of inorganic chemistry, which are broadly studied as coordination compounds and are gradually becoming more important in biochemical and analytical applications.

    METHODS: They have also been used for antibacterial, antifungal, anticancer, antitubercular activities. Novel synthesised Schiff's base 2-methoxy-4-((3-methylpyridin-2-ylimino)methyl)phenol (SB) and its metal complexes (Zn[II], Cu[II], Co[II] and Ni[II]) were characterised by UV, IR and NMR spectroscopy. Formation of the Schiff base and the metal (Zn[II], Cu[II], Co[II] and Ni[II]) chelates was supported by spectral and analytical data. The ligand and metal complexes have been screened for their antibacterial activity against Staphylococcus aureus, Salmonella typhi, Escherichia coli, Klebsiella pneumoniae and antifungal activity against the fungi Candida albicans and Aspergillus niger. Further, the synthesised compounds were also screened for antiproliferative activity against the human colorectal carcinoma (HCT116) cell line using the Sulforhodamine B assay.

    RESULT: Metal complexes formed were found to enhance the potency of the Schiff base due to coordination with a copper complex, showing better activity than others.

    CONCLUSION: Copper complex was observed to be more potent than other complexes against all the pathogenic microbes and cancer cell line (HCT116).

    Matched MeSH terms: HCT116 Cells
  14. Nazir M, Abbasi MA, Aziz-Ur-Rehman -, Siddiqui SZ, Ali Shah SA, Shahid M, et al.
    Pak J Pharm Sci, 2019 Nov;32(6):2585-2597.
    PMID: 31969290
    In the study presented here, the nucleophilic substitution reaction of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide was carried out with different alkyl/aralkyl halides (5a-r) to form its different S-substituted derivatives (6a-r), as depicted in scheme 1. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR and CHN analysis data. Bacterial biofilm inhibitory activity of all the synthesized compounds was carried out against Bacillus subtilis and Escherichia coli. The anticancer activity of these molecules was ascertained using anti-proliferation (SRB) assay on HCT 116 Colon Cancer Cell lines while the cytotoxicity of these molecules was profiled for their haemolytic potential. From this investigation it was rational that most of the compounds exhibited suitable antibacterial and anticancer potential along with a temperate cytotoxicity.
    Matched MeSH terms: HCT116 Cells/drug effects
  15. Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM
    PMID: 24607427 DOI: 10.1016/j.saa.2014.01.086
    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.
    Matched MeSH terms: HCT116 Cells
  16. Kumari M, Tahlan S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2021 Jan 21;15(1):5.
    PMID: 33478538 DOI: 10.1186/s13065-020-00717-y
    BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

    METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

    RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).

    Matched MeSH terms: HCT116 Cells
  17. Hajiaghaalipour F, Faraj FL, Bagheri E, Ali HM, Abdulla MA, Majid NA
    Curr Pharm Des, 2017;23(41):6358-6365.
    PMID: 28325143 DOI: 10.2174/1381612823666170321093345
    BACKGROUND: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.

    METHODS: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.

    RESULTS: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.

    CONCLUSION: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.

    Matched MeSH terms: HCT116 Cells
  18. Goh BH, Chan CK, Kamarudin MN, Abdul Kadir H
    J Ethnopharmacol, 2014 Apr 28;153(2):375-85.
    PMID: 24613274 DOI: 10.1016/j.jep.2014.02.036
    Swietenia macrophylla King is a traditional herb used to treat various diseases including hypertension, diabetes and cancer. Previous study demonstrated its anti-tumor effect but the potential mechanisms have not been clearly defined. The current study was to further investigate the underlying mechanism of ethyl acetate fraction of Swietenia macrophylla (SMEAF)-induced anti-proliferative effect and apoptosis in HCT116 colorectal carcinoma cell.
    Matched MeSH terms: HCT116 Cells
  19. Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2019 02 28;9(1):3056.
    PMID: 30816228 DOI: 10.1038/s41598-019-39592-6
    A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
    Matched MeSH terms: HCT116 Cells
  20. Ser HL, Palanisamy UD, Yin WF, Chan KG, Goh BH, Lee LH
    Sci Rep, 2016 Apr 13;6:24247.
    PMID: 27072394 DOI: 10.1038/srep24247
    Actinobacteria from the unique intertidal ecosystem of the mangroves are known to produce novel, bioactive secondary metabolites. A novel strain known as MUSC 136(T) (=DSM 100712(T) = MCCC 1K01246(T)) which was isolated from Malaysian mangrove forest soil has proven to be no exception. Assessed by a polyphasic approach, its taxonomy showed a range of phylogenetic and chemotaxonomic properties consistent with the genus of Streptomyces. Phylogenetically, highest similarity was to Streptomyces misionensis NBRC 13063(T) (99.6%) along with two other strains (>98.9% sequence similarities). The DNA-DNA relatedness between MUSC 136(T) and these type strains ranged from 22.7 ± 0.5% to 46.5 ± 0.2%. Overall, polyphasic approach studies indicated this strain represents a novel species, for which the name Streptomyces malaysiense sp. nov. is proposed. The potential bioactivities of this strain were explored by means of antioxidant and cytotoxic assays. Intriguingly, MUSC 136(T) exhibited strong antioxidative activities as evaluated by a panel of antioxidant assays. It was also found to possess high cytotoxic effect against HCT-116 cells, which probably mediated through altering p53 protein and intracellular glutathione levels. Chemical analysis of the extract using GC-MS further affirms that the strain produces chemopreventive related metabolites.
    Matched MeSH terms: HCT116 Cells
Filters
Contact Us

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

External Links