MyMedR

Displaying publications 1 - 20 of 48 in total

Abstract:

Sort:

Biogenic Synthesis, Characterization and Evaluation of Silver Nanoparticles from Aspergillus niger JX556221 Against Human Colon Cancer Cell Line HT-29

Chengzheng W, Jiazhi W, Shuangjiang C, Swamy MK, Sinniah UR, Akhtar MS, et al.

J Nanosci Nanotechnol, 2018 May 01;18(5):3673-3681.
PMID: 29442882 DOI: 10.1166/jnn.2018.15364

Nanobiotechnology has emerged as a promising technology to develop new therapeutically active nanomaterials. The present study was aimed to biosynthesize AgNPs extracellularly using Aspergillus niger JX556221 fungal extract and to evaluate their anticancer potential against colon cancer cell line, HT-29. UV-visible spectral characterization of the synthesized AgNPs showed higher absorption peak at 440 nm wavelength. Transmission Electron Microscopy (TEM) analysis revealed the monodispersed nature of synthesized AgNPs occurring in spherical shape with a size in the range of 20-25 nm. Further, characterization using Energy Dispersive Spectroscopy (EDX) confirmed the face-centred cubic crystalline structure of metallic AgNPs. FTIR data revealed the occurrence of various phytochemicals in the cell free fungal extract which substantiated the fungal extract mediated AgNPs synthesis. The cytotoxic effect of AgNPs was studied by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results evidenced the cytotoxic effect of AgNPs on HT-29 cell lines in a dose dependent manner. The highest activity was found at 100 μg/ml concentration after 24 h of incubation. Use of propidium iodide staining examination method confirmed the cytotoxic effect of AgNPs through inducing cell apoptosis. AgNPs cytotoxicity was found to be through elevating reactive oxygen species (ROS), and caspase-3 activation resulting in induced apoptosis. Therefore, this research finding provides an insight towards the development of novel anticancer agents using biological sources.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Signal transducer and activator of transcription 3 - a promising target in colitis-associated cancer

Pandurangan AK, Esa NM

Asian Pac J Cancer Prev, 2014;15(2):551-60.
PMID: 24568457

Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)- κB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, Wnt/β-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
In Vitro Anticancer Activity of Au, Ag Nanoparticles Synthesized Using Commelina nudiflora L. Aqueous Extract Against HCT-116 Colon Cancer Cells

Kuppusamy P, Ichwan SJ, Al-Zikri PN, Suriyah WH, Soundharrajan I, Govindan N, et al.

Biol Trace Elem Res, 2016 Oct;173(2):297-305.
PMID: 26961292 DOI: 10.1007/s12011-016-0666-7

Recently, metal nanoparticles have been getting great medical and social interests due to their potential physico-chemical properties such as higher affinity, low molecular weight, and larger surface area. The biosynthesized gold and silver nanoparticles are spherical, triangular in shape with an average size of 24-150 nm as reported in our earlier studies. The biological properties of synthesized gold and silver nanoparticles are demonstrated in this paper. The different in vitro assays such as MTT, flow cytometry, and reverse transcription polymerase chain reaction (RT-qPCR) techniques were used to evaluate the in vitro anticancer properties of synthesized metal nanoparticles. The biosynthesized gold and silver nanoparticles have shown reduced cell viability and increased cytotoxicity in HCT-116 colon cancer cells with IC50 concentration of 200 and 100 μg/ml, respectively. The flow cytometry experiments revealed that the IC50 concentrations of gold and silver nanoparticle-treated cells that have significant changes were observed in the sub-G1 cell cycle phase compared with the positive control. Additionally, the relative messenger RNA (mRNA) gene expressions of HCT-116 cells were studied by RT-qPCR techniques. The pro-apoptotic genes such as PUMA (++), Caspase-3 (+), Caspase-8 (++), and Caspase-9 (++) were upregulated in the treated HCT-116 cells compared with cisplatin. Overall, these findings have proved that the synthesized gold and silver nanoparticles could be potent anti-colon cancer drugs.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Adjuvant chemotherapy and radiotherapy in the management of colorectal cancer

Lim Kok Hooi A

Gan To Kagaku Ryoho, 1992 Jul;19(8 Suppl):1233-5.
PMID: 1514837
Matched MeSH terms: Colonic Neoplasms/drug therapy
Potential of Gold Candidates against Human Colon Cancer

Abbasi M, Yaqoob M, Haque RA, Iqbal MA

Mini Rev Med Chem, 2021;21(1):69-78.
PMID: 32767935 DOI: 10.2174/1389557520666200807130721

Development of novel metallodrugs with pharmacological profile plays a significant role in modern medicinal chemistry and drug design. Metal complexes have shown remarkable clinical results in current cancer therapy. Gold complexes have attained attention due to their high antiproliferative potential. Gold-based drugs are used for the treatment of rheumatoid arthritis. Gold-containing compounds with selective and specific targets are capable to assuage the symptoms of a range of human diseases. Gold (I) species with labile ligands (such as Cl in TEPAuCl) interact with isolated DNA; therefore, this biomolecule has been considered as a target for gold drugs. Gold (I) has a high affinity towards sulfur and selenium. Due to this, gold (I) drugs readily interact with cysteine or selenocysteine residue of the enzyme to form protein-gold(I) thiolate or protein-gold (I) selenolate complexes that lead to inhibition of the enzyme activity. Au(III) compounds due to their square-planner geometriesthe same as found in cisplatin, represent a good source for the development of anti-tumor agents. This article aims to review the most important applications of gold products in the treatment of human colon cancer and to analyze the complex interplay between gold and the human body.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells

Ng PL, Rajab NF, Then SM, Mohd Yusof YA, Wan Ngah WZ, Pin KY, et al.

J Zhejiang Univ Sci B, 2014 Aug;15(8):692-700.
PMID: 25091987 DOI: 10.1631/jzus.B1300303

OBJECTIVE: The combination effect of Piper betle (PB) and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated.
METHODS: HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography (HPLC) was performed to exclude any possible chemical interaction between the compounds.
RESULTS: In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose (IC50 12.5 µmol/L) and a shorter time (24 h) in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively.
CONCLUSIONS: In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
KEYWORDS: 5-Fluorouracil; Herb-drug interaction; Isobologram analysis; Piper betle L.; Piperaceae

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo

Hashim YZ, Worthington J, Allsopp P, Ternan NG, Brown EM, McCann MJ, et al.

Food Funct, 2014 Jul 25;5(7):1513-9.
PMID: 24836598 DOI: 10.1039/c4fo00090k

The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Pectin matrix as oral drug delivery vehicle for colon cancer treatment

Wong TW, Colombo G, Sonvico F

AAPS PharmSciTech, 2011 Mar;12(1):201-14.
PMID: 21194013 DOI: 10.1208/s12249-010-9564-z

Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats

Norazalina S, Norhaizan ME, Hairuszah I, Norashareena MS

Exp. Toxicol. Pathol., 2010 May;62(3):259-68.
PMID: 19464858 DOI: 10.1016/j.etp.2009.04.002

This study is carried out to determine the potential of phytic acid extracted from rice bran in the suppression of colon carcinogenesis induced by azoxymethane (AOM) in rats. Seventy-two male Sprague-Dawley rats were divided into 6 groups with 12 rats in each group. The intended rats for cancer treatment received two intraperitoneal injections of AOM in saline (15mg/kg bodyweight) over a 2-week period. The treatments of phytic acid were given in two concentrations: 0.2% (w/v) and 0.5% (w/v) during the post-initiation phase of carcinogenesis phase via drinking water. The colons of the animals were analyzed for detection and quantification of aberrant crypt foci (ACF) after 8 weeks of treatment. The finding showed treatment with 0.2% (w/v) extract phytic acid (EPA) gave the greatest reduction in the formation of ACF. In addition, phytic acid significantly suppressed the number of ACF in the distal, middle and proximal colon as compared to AOM alone (p<0.05). For the histological classification of ACF, treatment with 0.5% (w/v) commercial phytic acid (CPA) had the highest percentage (71%) of non-dysplastic ACF followed by treatment with 0.2% (w/v) EPA (61%). Administration of phytic acid also reduced the incidence and multiplicity of total tumors even though there were no significant differences between groups. In conclusion, this study found the potential value of phytic acid extracted from rice bran in reducing colon cancer risk in rats.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by increasing invasiveness and resistance against doxorubicin-induced apoptosis

Chieng CK, Say YH

Tumour Biol., 2015 Sep;36(10):8107-20.
PMID: 25983001 DOI: 10.1007/s13277-015-3530-z

As the cellular prion protein (PrP(C)) has been implicated in carcinogenesis, we aimed to investigate the effects of cancer cell-specific PrP(C) overexpression from the invasion, metastasis, and apoptosis aspects, by performing cell motility assays, cell proliferation assays under anchorage-dependent and anchorage-independent conditions, and apoptosis evasion when subjected to multiple anti-cancer drugs. Overexpression of PrP(C) in LS 174T was achieved by stable transfection. PrP(C) overexpression was shown to increase cell proliferation in anchorage-dependent and anchorage-independent manners, as shown by more viable cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, more colonies formed in soft agar assay and increased resistance to anoikis in poly-2-hydroxyethyl methacrylate-coated surface. PrP(C) overexpression also increased cell motility and invasiveness of LS 174T. Cell adhesion to extracellular matrix using collagen- and fibronectin-coated surfaces revealed increased cell attachment in LS 174T cells overexpressing PrP(C). Analysis of apoptotic and necrotic cells by propidium iodide/annexin V-fluorescein isothiocyanate microscopy and 7-amino-actinomycin D/annexin V-phycoerythrin flow cytometry revealed that PrP(C) overexpression attenuated doxorubicin-induced apoptosis. Human apoptosis antibody array with 35 apoptosis-related proteins revealed that three inhibitor of apoptosis proteins (IAPs)-survivin, X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein-1 (cIAP-1)-were upregulated in LS 174T cells overexpressing PrP(C) in doxorubicin-induced apoptosis. In conclusion, the overexpression of PrP(C) could enhance the invasiveness and survival of LS 174T colorectal cancer cells, indicating that PrP(C) plays a role in colorectal cancer biology.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Polymeric Microsphere Formulation for Colon Targeted Delivery of 5-Fluorouracil Using Biocompatible Natural Gum Katira

Karan S, Choudhury H, Chakra BK, Chatterjee TK

Asian Pac J Cancer Prev, 2019 07 01;20(7):2181-2194.
PMID: 31350983 DOI: 10.31557/APJCP.2019.20.7.2181

Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped
delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance
and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop
and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal
therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal
model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the
natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology,
encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric
microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle
with size ranged from 210.37±7.50 to 314.45±7.80 μm.Targeted microsphere exhibited good cytotoxicity and also has
high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we
foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient
colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Evaluation of Anti-Tumorigenic Effects of Diosmetin against Human Colon Cancer Xenografts in Athymic Nude Mice

Koosha S, Mohamed Z, Sinniah A, Alshawsh MA

Molecules, 2019 Jul 10;24(14).
PMID: 31295840 DOI: 10.3390/molecules24142522

Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.

Matched MeSH terms: Colonic Neoplasms/drug therapy
The influence of R substituents in triphenylphosphinegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh] (R=Me, Et and iPr), upon in vitro cytotoxicity against the HT-29 colon cancer cell line and upon apoptotic pathways

Yeo CI, Ooi KK, Akim AM, Ang KP, Fairuz ZA, Halim SN, et al.

J Inorg Biochem, 2013 Oct;127:24-38.
PMID: 23850666 DOI: 10.1016/j.jinorgbio.2013.05.011

The Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with 1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound 1 activates the p73 gene, whereas each of 2 and 3 activates the p53 gene. An additional apoptotic mechanism is exhibited by 2, that is, via the JNK/MAP pathway.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Pharmacokinetic and anti-colon cancer properties of curcumin-containing chitosan-pectinate composite nanoparticles

Alkhader E, Roberts CJ, Rosli R, Yuen KH, Seow EK, Lee YZ, et al.

J Biomater Sci Polym Ed, 2018 12;29(18):2281-2298.
PMID: 30376409 DOI: 10.1080/09205063.2018.1541500

Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6 hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

Khalid AQ, Bhuvanendran S, Magalingam KB, Ramdas P, Kumari M, Radhakrishnan AK

Nutrients, 2021 Nov 12;13(11).
PMID: 34836311 DOI: 10.3390/nu13114056

The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Fulltext Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo

Al-Henhena N, Khalifa SA, Ying RP, Ismail S, Hamadi R, Shawter AN, et al.

BMC Complement Altern Med, 2015;15(1):419.
PMID: 26608653 DOI: 10.1186/s12906-015-0926-7

With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Human colon cancer targeted pro-apoptotic, anti-metastatic and cytostatic effects of binuclear Silver(I)-N-Heterocyclic carbene (NHC) complexes

Asif M, Iqbal MA, Hussein MA, Oon CE, Haque RA, Khadeer Ahamed MB, et al.

Eur J Med Chem, 2016 Jan 27;108:177-187.
PMID: 26649905 DOI: 10.1016/j.ejmech.2015.11.034

The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue

Goh TB, Koh RY, Mordi MN, Mansor SM

Asian Pac J Cancer Prev, 2014;15(14):5659-65.
PMID: 25081682

BACKGROUND: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro.
MATERIALS AND METHODS: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively.
RESULTS: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 μM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60).
CONCLUSIONS: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract

Aisha AF, Abu-Salah KM, Ismail Z, Majid AM

BMC Complement Altern Med, 2012;12:104.
PMID: 22818000

BACKGROUND: Xanthones are a group of oxygen-containing heterocyclic compounds with remarkable pharmacological effects such as anti-cancer, antioxidant, anti-inflammatory, and antimicrobial activities.
METHODS: A xanthones extract (81% α-mangostin and 16% γ-mangostin), was prepared by crystallization of a toluene extract of G. mangostana fruit rinds and was analyzed by LC-MS. Anti-colon cancer effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicity, apoptosis, anti-tumorigenicity, and effect on cell signalling pathways. The in vivo anti-colon cancer activity was also investigated on subcutaneous tumors established in nude mice.
RESULTS: The extract showed potent cytotoxicity (median inhibitory concentration 6.5 ± 1.0 μg/ml), due to induction of the mitochondrial pathway of apoptosis. Three key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity, were also inhibited. The extract and α-mangostin up-regulate the MAPK/ERK, c-Myc/Max, and p53 cell signalling pathways. The xanthones extract, when fed to nude mice, caused significant growth inhibition of the subcutaneous tumor of HCT 116 colorectal carcinoma cells.
CONCLUSIONS: Our data suggest new mechanisms of action of α-mangostin and the G. mangostana xanthones, and suggest the xanthones extract of as a potential anti-colon cancer candidate.

Matched MeSH terms: Colonic Neoplasms/drug therapy*
Apoptosis induction, cell cycle arrest and in vitro anticancer activity of gonothalamin in a cancer cell lines

Alabsi AM, Ali R, Ali AM, Al-Dubai SA, Harun H, Abu Kasim NH, et al.

Asian Pac J Cancer Prev, 2012;13(10):5131-6.
PMID: 23244123

Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.

Matched MeSH terms: Colonic Neoplasms/drug therapy

Filters

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

External Links