Displaying publications 21 - 40 of 72 in total

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  1. Limonin modulated immune and inflammatory responses to suppress colorectal adenocarcinoma in mice model
    Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM
    Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
    PMID: 34009457 DOI: 10.1007/s00210-021-02101-6
    Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p 
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  2. Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial
    Golkhalkhali B, Rajandram R, Paliany AS, Ho GF, Wan Ishak WZ, Johari CS, et al.
    Asia Pac J Clin Oncol, 2018 Jun;14(3):179-191.
    PMID: 28857425 DOI: 10.1111/ajco.12758
    AIM: Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy.

    METHODS: A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein.

    RESULTS: The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004).

    CONCLUSION: The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy.

    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  3. Fulltext Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer
    Ismail NI, Othman I, Abas F, H Lajis N, Naidu R
    Int J Mol Sci, 2019 May 17;20(10).
    PMID: 31108984 DOI: 10.3390/ijms20102454
    Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy
  4. Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells
    Hakim L, Alias E, Makpol S, Ngah WZ, Morad NA, Yusof YA
    Asian Pac J Cancer Prev, 2014;15(11):4651-7.
    PMID: 24969899
    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  5. Fulltext In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells
    Leong SW, Chia SL, Abas F, Yusoff K
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858795 DOI: 10.3390/molecules25173877
    In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  6. Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review
    Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2014;15(14):5501-8.
    PMID: 25081655
    Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti- inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/β-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  7. High frequency of hand foot syndrome with capecitabine
    Kamil M, Haron M, Yosuff N, Khalid I, Azman N
    J Coll Physicians Surg Pak, 2010 Jun;20(6):421-2.
    PMID: 20642979 DOI: 06.2010/JCPSP.421422
    A hospital based cross-sectional retrospective study was conducted to determine the frequency of hand foot syndrome (HFS) with Capecitabine as a single agent and in combination with Oxaliplatin. The study included 43 consecutive cases of colorectal carcinoma and conducted from June till December 2008. Patients on palliative care were excluded. SPSS was used for the application of chi-square test, by keeping the level of significance as p < 0.05. Fifteen (34.9%) patients developed HFS, 10 in the single-agent and 5 in the combination group. No significant association of HFS with either regimens was noted (p=0.876).
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  8. Modulation of cell growth and PPARgamma expression in human colorectal cancer cell lines by ciglitazone
    Yaacob NS, Darus HM, Norazmi MN
    Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.
    PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006
    Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  9. Fulltext Vanillin differentially affects azoxymethane-injected rat colon carcinogenesis and gene expression
    Ho KL, Chong PP, Yazan LS, Ismail M
    J Med Food, 2012 Dec;15(12):1096-102.
    PMID: 23216109 DOI: 10.1089/jmf.2012.2245
    Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  10. Fulltext Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest
    Chan CK, Chan G, Awang K, Abdul Kadir H
    Molecules, 2016 Mar 21;21(3):385.
    PMID: 27007366 DOI: 10.3390/molecules21030385
    Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay-guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose-dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose-dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  11. Adjuvant treatment in colorectal cancer. Experience from a referral center in eastern peninsular Malaysia
    Biswal BM, Sain AH, Othman NH, Baba A
    Trop Gastroenterol, 2002 Jul-Sep;23(3):134-7.
    PMID: 12693156
    Colorectal cancer is one of the most common malignancies in the West, but in Asia the incidence is low. However in Malaysia, colorectal cancer is increasing with a reported figure of 15% of all cancer cases. Adjuvant chemo and radiotherapy are now more frequently used in such patients. The present retrospective analysis was performed to document the effect of such therapy among patients with colorectal cancer in Malaysia.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  12. Schiff base-nickel, palladium, and platinum complexes derived from N-cyclohexyl hydrazine carbothioamide and 3-hydroxy-4-methoxybenzaldehyde: Selective antiproliferative and proapoptotic effects against colorectal carcinoma
    Arafath MA, Al-Suede FSR, Adam F, Al-Juaid S, Khadeer Ahamed MB, Majid AMSA
    Drug Dev Res, 2019 09;80(6):778-790.
    PMID: 31215682 DOI: 10.1002/ddr.21559
    The bidentate N-cyclohexyl-2-(3-hydroxy-4-methoxybenzylidene)hydrazine-1-carbothioamide Schiff base ligand (HL) was coordinated to divalent nickel, palladium and platinum ions to form square planar complexes. The nickel and palladium complexes, [NiL2 ], [PdL2 ] form square planar complexes with 2:1 ligand to metal ratio. The platinum complex, [PtL(dmso)Cl] formed a square planar complex with 1:1 ligand to metal ratio. Platinum undergoes in situ reaction with DMSO before complexing with the ligand in solution. The cytotoxicity of HL, [NiL2 ], [PdL2 ], and [PtL(dmso)Cl] were evaluated against human colon cancer cell line (HCT-116), human cervical cancer (Hela) cell line, melanoma (B16F10) cells, and human normal endothelial cell lines (Eahy926) by MTT assay. The [NiL2 ] complex displayed selective cytotoxic effect against the HCT 116 cancer cell line with IC50 of 7.9 ± 0.2 μM. However, HL, [PdL2 ], and [PtL(dmso)Cl] only exhibited moderate cytotoxic activity with IC50 = 75.9 ± 2.4, 100.0 ± 1.8, and 101.0 ± 3.6 μM, respectively. The potent cytotoxicity of [NiL2 ] was characterized using Hoechst and Rhodamine assays. The nickel complex, [NiL2 ], caused remarkable nuclear condensation and reduction in mitochondrial membrane potential. In addition, molecular docking studies confirms that [NiL2 ] possesses significant binding efficiency with Tyrosine kinase. Altogether, the results revealed that [NiL2 ] exhibits cytotoxicity against the cancer cells via Tyrosine kinase-induced proapoptosis pathway. This study demonstrates that the [NiL2 ] complex could be a promising therapeutic agent against colorectal carcinoma.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy
  13. Synthesis and in-vitro anti-cancer evaluations of multi-methoxylated asymmetrical diarylpentanoids as intrinsic apoptosis inducer against colorectal cancer
    Leong SW, Chia SL, Abas F, Yusoff K
    Bioorg Med Chem Lett, 2020 04 15;30(8):127065.
    PMID: 32127259 DOI: 10.1016/j.bmcl.2020.127065
    In the present study, a series of nine stable 3,4,5-methoxylphenyl-containing asymmetrical diarylpentanoids, derivatives of curcuminoids, have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, LoVo and SW620, HT29, RKO and NCI-H508, respectively. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-hydroxyl and adjacent dimethoxyl groups are crucial for enhanced cytotoxicity of diarylpentanoids. Among the evaluated analogs, 8 has been identified as the lead compound due to its highest chemotherapeutic index of 9.9 and nano molar scale cytotoxicity against SW620 and RKO. Colonies formation and cell cycle analyses on 8-treated RKO cells showed that 8 exhibits strong anti-proliferative activity by inducing G2/M-phase cell arrest. Subsequent flow cytometry based annexin-V and DCFHDA studies suggested that 8 could induce apoptosis through intracellular ROS-dependent pathway. Further Western blot studies confirmed that 8 has induced intrinsic apoptosis in RKO cells through the up-regulations of Bad and Bax pro-apoptotic proteins and down-regulations of Bcl-2 and Bcl-xL pro-survival proteins. In all, the present results suggest that 8 could be a potent lead which deserves further modification and investigation in the development of small molecule-based anti-colorectal cancer agents.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  14. Fulltext Green Synthesized Montmorillonite/Carrageenan/Fe3O4 Nanocomposites for pH-Responsive Release of Protocatechuic Acid and Its Anticancer Activity
    Yew YP, Shameli K, Mohamad SE, Lee KX, Teow SY
    Int J Mol Sci, 2020 Jul 09;21(14).
    PMID: 32659939 DOI: 10.3390/ijms21144851
    Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) was used as matrix support, while Fe3O4 nanoparticles (NPs) and carrageenan (CR) were used as filler and stabilizer, respectively. The combination of these materials resulted in a novel nanocomposite (MMT/CR/Fe3O4-NCs). A series of characterization experiments was conducted. The purity of MMT/CR/Fe3O4-NCs was confirmed by X-ray diffraction (XRD) analysis. High resolution transmission electron microscopy (HRTEM) analysis revealed the uniform and spherical shape of Fe3O4 NPs with an average particle size of 9.3 ± 1.2 nm. Vibrating sample magnetometer (VSM) analysis showed an Ms value of 2.16 emu/g with negligible coercivity which confirmed the superparamagnetic properties. Protocatechuic acid (PCA) was loaded onto the MMT/CR/Fe3O4-NCs and a drug release study showed that 15% and 92% of PCA was released at pH 7.4 and 4.8, respectively. Cytotoxicity assays showed that both MMT/CR/Fe3O4-NCs and MMT/CR/Fe3O4-PCA effectively killed HCT116 which is a colorectal cancer cell line. Dose-dependent inhibition was seen and the killing was enhanced two-fold by the PCA-loaded NCs (IC50-0.734 mg/mL) compared to the unloaded NCs (IC50-1.5 mg/mL). This study highlights the potential use of MMT/CR/Fe3O4-NCs as a biologically active pH-responsive drug delivery agent. Further investigations are warranted to delineate the mechanism of cell entry and cancer cell killing as well as to improve the therapeutic potential of MMT/CR/Fe3O4-NCs.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy
  15. Heterogeneity in cancer cells: variation in drug response in different primary and secondary colorectal cancer cell lines in vitro
    Arul M, Roslani AC, Cheah SH
    In Vitro Cell Dev Biol Anim, 2017 May;53(5):435-447.
    PMID: 28120247 DOI: 10.1007/s11626-016-0126-x
    Tumor heterogeneity may give rise to differential responses to chemotherapy drugs. Therefore, unraveling tumor heterogeneity has an implication for biomarker discovery and cancer therapeutics. To test this phenomenon, we investigated the differential responses of three secondary colorectal cancer cell lines of different origins (HCT116, HT29, and SW620 cells) and four novel primary cell lines obtained from different colorectal cancer patients to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) and explored the differences in gene expression among the primary cell lines in response to exposure to cytotoxic drugs. Cells were exposed to different doses of 5-FU and L-OHP separately or in combinations of equitoxic drug or equimolar drug ratios (median effect of Chou-Talalay principle). Cell viability was assessed using MTT assay and the respective IC50values were determined. Changes in gene expression in primary cell lines after exposure to the same drug doses were compared using real-time PCR array. The sensitivities (IC50) of different cell lines, both secondary and primary, to 5-FU and L-OHP were significantly different, whether in monotherapy or combined treatment. Primary cell lines needed higher doses to reach IC50. There were variations in gene expression among the primary cell lines of different chemosensitivities to the challenge of the same combined dose of 5-FU and L-OHP. The results confirm the heterogeneous nature of colorectal cancer cells from different patient tumors. Studies using primary cancer cells established from patient's tumors rather than secondary cell lines will more closely reflect the actual character of the disease.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  16. Fulltext Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116
    Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Molecules, 2021 Jan 13;26(2).
    PMID: 33450878 DOI: 10.3390/molecules26020376
    Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 ± 0.89 µg/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 ± 3.12 µg/mL) and silymarin (>200 µg/mL). Further analyses exhibited that berberine treatment caused G0/G1 phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  17. Fulltext pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
    Biabanikhankahdani R, Alitheen NBM, Ho KL, Tan WS
    Sci Rep, 2016 11 24;6:37891.
    PMID: 27883070 DOI: 10.1038/srep37891
    Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy
  18. Colorectal, Prostate and Pancreas Human Cancers Targeted Bioassay-guided Isolations and Characterization of Chemical Constituents from Tephrosia apollinea
    Hassan LEA, Iqbal MA, Dahham SS, Tabana YM, Ahamed MBK, Majid AMSA
    Anticancer Agents Med Chem, 2017;17(4):590-598.
    PMID: 27671298 DOI: 10.2174/1871520616666160926113711
    BACKGROUND: Cancer is characterized by uncontrolled cell division caused by dysregulation of cell proliferation. Therefore, agents that impair cancer cell proliferation could have potential therapeutic value. Higher plants are considered to be a good source of anticancer agents, and several clinically tested chemotherapeutic agents have been isolated from plants or derived from constituents of plant origin.

    METHODS: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast).

    RESULTS: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells.

    CONCLUSION: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies.

    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  19. Oral Cryotherapy: Prevention of Oral Mucositis and Pain Among Patients With Colorectal Cancer Undergoing Chemotherapy
    Idayu Mat Nawi R, Lei Chui P, Wan Ishak WZ, Hsien Chan CM
    Clin J Oncol Nurs, 2018 10 01;22(5):555-560.
    PMID: 30239519 DOI: 10.1188/18.CJON.555-560
    BACKGROUND: Evidence remains mixed on the benefits of oral cryotherapy in the prevention of oral mucositis and pain associated with fluorouracil-based chemotherapy.

    OBJECTIVES: The intent of this article is to evaluate the effect of oral cryotherapy on the prevention of oral mucositis and pain among patients with colorectal cancer undergoing fluorouracil-based chemotherapy.

    METHODS: Using an experimental study design, the authors randomly assigned 80 patients to either the intervention (n = 40) or usual care group (n = 40). Intervention group participants received oral cryotherapy in the form of ice chips held in their mouths during chemotherapy infusion. Both groups used sodium bicarbonate mouthwash postchemotherapy until the next cycle.

    FINDINGS: In the usual care group, most participants reported grade 2 (moderate to life-threatening) or greater mucositis. Pain associated with mucositis was lower using oral cryotherapy, with the majority of participants in the intervention group reporting no pain.

    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  20. Novel 2-Benzoyl-6-(2,3-Dimethoxybenzylidene)-Cyclohexenol Confers Selectivity toward Human MLH1 Defective Cancer Cells through Synthetic Lethality
    Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.
    SLAS Discov, 2019 06;24(5):548-562.
    PMID: 30897027 DOI: 10.1177/2472555219831405
    DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
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