Displaying publications 41 - 60 of 97 in total

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  1. Rengarajan T, Yaacob NS
    Eur J Pharmacol, 2016 Oct 15;789:8-16.
    PMID: 27377217 DOI: 10.1016/j.ejphar.2016.07.001
    Epidemiological studies show that consumption of diets rich in fruits and vegetables is associated with lower risks of cancer. This evidence has kindled interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds is fisetin (3,7,3,4-tetrahydroxyflavone), a flavonol that is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. Fisetin has been shown to inhibit or retard the growth of various cancer cells in culture and implanted tumors in vivo. Fisetin targets many components of intracellular signaling pathways including regulators of cell survival and apoptosis, tumor angiogenic and metastatic switches by modulating a distinct set of upstream kinases, transcription factors and their regulators. Current evidence supports the idea that fisetin is a promising agent for cancer treatment. This review summarizes reported anticancer effects of fisetin, and re-emphasizes its potential therapeutic role in the treatment of cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  2. Sonali, Singh RP, Sharma G, Kumari L, Koch B, Singh S, et al.
    Colloids Surf B Biointerfaces, 2016 Nov 01;147:129-141.
    PMID: 27497076 DOI: 10.1016/j.colsurfb.2016.07.058
    The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes, which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and electrospray ionisation (ESI) mass spectroscopy (ESI-MS). The theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release study. Biocompatibility and safety of theranostic liposomes were studied by reactive oxygen species (ROS) generation study and histopathology of brain. In-vivo study was performed for determination of brain theranostic effects in comparison with marketed formulation (Docel™) and free QDs. The particle sizes of the non-targeted and targeted theranostic liposomes were found in between 100 and 200nm. About 70% of drug encapsulation efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated liposomes was sustained for more than 72h with 80% of drug release. The in-vivo results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and 6.98-fold more effective than Docel™ after 2h and 4h treatments, respectively. Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation effectively, and did not show any signs of brain damage or edema in brain histopathology. The results of this study have indicated that RGD-TPGS decorated theranostic liposomes are promising carrier for brain theranostics.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  3. Tan KX, Danquah MK, Sidhu A, Ongkudon CM, Lau SY
    Eur J Pharm Sci, 2017 Jan 01;96:8-19.
    PMID: 27593990 DOI: 10.1016/j.ejps.2016.08.061
    Cancer is a leading cause of global mortality. Whilst anticancer awareness programs have increased significantly over the years, scientific research into the development of efficient and specific drugs to target cancerous cells for enhanced therapeutic effects has not received much clinical success. Chemotherapeutic agents are incapable of acting specifically on cancerous cells, thus causing low therapeutic effects accompanied by toxicity to surrounding normal tissues. The search for smart, highly specific and efficient cancer treatments and delivery systems continues to be a significant research endeavor. Targeted cancer therapy is an evolving treatment approach with great promise in enhancing the efficacy of cancer therapies via the delivery of therapeutic agents specifically to and into desired tumor cells using viral or non-viral targeting elements. Viral oncotherapy is an advanced cancer therapy based on the use of oncolytic viruses (OV) as elements to specifically target, replicate and kill malignant cancer cells selectively without affecting surrounding healthy cells. Aptamers, on the other hand, are non-viral targeting elements that are single-stranded nucleic acids with high specificity, selectivity and binding affinity towards their cognate targets. Aptamers have emerged as a new class of bioaffinity targeting elements can be generated and molecularly engineered to selectively bind to diverse targets including proteins, cells and tissues. This article discusses, comparatively, the potentials and impacts of both viral and aptamer-mediated targeted cancer therapies in advancing conventional drug delivery systems through enhanced target specificity, therapeutic payload, bioavailability of the therapeutic agents at the target sites whilst minimizing systemic cytotoxicity. This article emphasizes on effective site-directed targeting mechanisms and efficacy issues that impact on clinical applications.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  4. Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  5. Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U
    Drug Discov Today, 2017 02;22(2):314-326.
    PMID: 27671487 DOI: 10.1016/j.drudis.2016.09.013
    Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  6. Nordin N, Kanagesan S, Zamberi NR, Yeap SK, Abu N, Tamilselvan S, et al.
    IET Nanobiotechnol, 2017 Apr;11(3):343-348.
    PMID: 28476993 DOI: 10.1049/iet-nbt.2016.0007
    In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol-gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X-ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17-41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB-231) and (MCF-7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB-231 and MCF-7 after being examined with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB-231 cell line than in MCF-7. Therefore, further cytotoxicity tests were performed on MDA MB-231 cell line.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  7. Petersen AB, Andersen NS, Konotop G, Hanafiah NH, Raab MS, Krämer A, et al.
    Eur J Med Chem, 2017 Apr 21;130:240-247.
    PMID: 28258034 DOI: 10.1016/j.ejmech.2017.02.055
    Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral and intravenous administration. Finally, 2'-benzylamine analogue 10 was confirmed to induce G2/M cell cycle arrest in vitro.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  8. Alkhader E, Billa N, Roberts CJ
    AAPS PharmSciTech, 2017 May;18(4):1009-1018.
    PMID: 27582072 DOI: 10.1208/s12249-016-0623-y
    In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  9. Lee WH, Loo CY, Leong CR, Young PM, Traini D, Rohanizadeh R
    Expert Opin Drug Deliv, 2017 08;14(8):937-957.
    PMID: 27759437 DOI: 10.1080/17425247.2017.1247804
    INTRODUCTION: The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer. Areas covered: This review focuses on the recent advances in the functionalization of nanocarriers with specific ligands, including antibodies, transferrin, folate, and peptides to overcome MDR cancer. The limitations of effective ligand-functionalized nanoparticles as well as therapeutic successes in ligand targeting are covered in the review. Expert opinion: Targeting MDR tumors with ligand-functionalized nanoparticles is a promising approach to improve the treatment of cancer. With this approach, higher drug concentrations at targeted sites would be achieved with lower dosage frequencies and reduced side effects in comparison to existing formulations of chemotherapeutic drugs. However, potential toxicities and immunological responses to ligands should be carefully reviewed for viable options in for future MDR cancer treatment.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  10. Birma Bwatanglang I, Mohammad F, Yusof NA, Elyani Mohammed N, Abu N, Alitheen NB, et al.
    J Mater Sci Mater Med, 2017 Aug 08;28(9):138.
    PMID: 28791524 DOI: 10.1007/s10856-017-5949-9
    5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs. The 5-FU@FACS-Mn:ZnS composite induced anti-proliferative properties in these organs as compared to the free 5-FU drug. Unlike the 5-FU@FACS-Mn:ZnS treated groups which showed some specific morphological changes such as cell shrinkage without obvious presence of adipocytes, the excised section of the tumor in the untreated control group and the free 5-FU drug treated group showed necrotic and degenerated cells; these cells are multifocally distributed in the tumor mass with evidence of widely distributed adipocytes within the tumor mass. These findings suggest that the 5-FU@FACS-Mn:ZnS composite has a superior role during the induction of apoptosis in the 4T1 cells as compared to the free 5-FU drug treated groups. The results of the study therefore suggest that the impregnation of 5-FU anti-cancer drug within the FACS-Mn:ZnS system significantly improves its selective targeting efficacy, in addition to improving the anti-proliferative properties and attenuate possible tumor resistances to the 5-FU drug. The work discusses about the anti-metastatic effects of folic acid-bound 5-Fluororacil loaded Mn:ZnS quantum dots towards 4T1 cell line proliferation in mice based on the histological analysis.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  11. Tan DM, Fu JY, Wong FS, Er HM, Chen YS, Nesaretnam K
    Nanomedicine (Lond), 2017 Oct;12(20):2487-2502.
    PMID: 28972460 DOI: 10.2217/nnm-2017-0182
    AIM: To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer.

    MATERIALS & METHODS: Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy.

    RESULTS: When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis.

    CONCLUSION: Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.

    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  12. Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Kura AU, Zakaria ZAB
    In Vitro Cell Dev Biol Anim, 2017 Dec;53(10):896-907.
    PMID: 28916966 DOI: 10.1007/s11626-017-0197-3
    Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p 
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  13. Ravichandiran V, Masilamani K, Senthilnathan B, Maheshwaran A, Wong TW, Roy P
    Curr Drug Deliv, 2017;14(8):1053-1059.
    PMID: 27572089 DOI: 10.2174/1567201813666160829100453
    BACKGROUND: Curcumin is a yellow polyphenolic chemopreventive agent isolated from the rhizomes of Curcuma longa. It is approved as Generally Regarded as Safe by US FDA. Nonetheless, its clinical success is limited due to its poor aqueous solubility, fast metabolism and short biological half-life attributes.

    OBJECTIVE: Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to overcome these biopharmaceutical drawbacks.

    METHODS: Curcumin liposomes with/without quercetin were prepared by lipid hydration technique. The liposomes were characterized for their particle size, zeta potential, surface morphology, drug loading and release characteristics. The toxicity of the liposomes were evaluated in-vitro and their invivo efficacy were tested against Dalton's ascites lymphoma in mice.

    RESULTS: Liposomes designed showed particle size of 261.8 ± 2.1 nm with a negative zeta potential of -22.6±1.6 mV. Quercetin decorated liposomes were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to those without quercetin. Similarly, the presence of quercetin also contributed to enhanced cytotoxicity of the liposomal formulation towards HT-29 cells and HCT-15 cells.

    CONCLUSION: Newer liposomal design exhibited promising potential to emerge as alternative anticancer therapeutics.

    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  14. Perumalsamy S, Aqilah Mohd Zin NA, Widodo RT, Wan Ahmad WA, Vethakkan SRDB, Huri HZ
    Curr Pharm Des, 2017;23(25):3689-3698.
    PMID: 28625137 DOI: 10.2174/1381612823666170616081256
    BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality.

    AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer.

    PATHOPHYSIOLOGY: Increased chemerin secretion activates an inflammatory response. The inflammatory response will increase the oxidative stress in adipose tissue and consequently results in an insulin-resistant state. The occurrence of inflammation, oxidative stress and insulin resistance leads to the progression of cancers.

    CONCLUSION: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.

    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  15. Kadivar A, Kamalidehghan B, Akbari Javar H, Karimi B, Sedghi R, Noordin MI
    Drug Des Devel Ther, 2017;11:469-481.
    PMID: 28260860 DOI: 10.2147/DDDT.S124102
    Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2-10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  16. Khan I, Kumar H, Mishra G, Gothwal A, Kesharwani P, Gupta U
    Curr Pharm Des, 2017;23(35):5315-5326.
    PMID: 28875848 DOI: 10.2174/1381612823666170829164828
    BACKGROUND: Delivery of chemotherapeutic drugs for the diagnosis and treatment of cancer is becoming advanced day by day. However, the challenge of the effective delivery system still does exist. In various types of cancers, breast cancer is the most commonly diagnosed cancer among women. Breast cancer is a combination of different diseases. It cannot be considered as only one entity because there are many specific patient factors, which are involved in the development of this disease. Nanotechnology has opened a new area in the effective treatment of breast cancer due to the several benefits offered by this technology.

    METHODS: Polymeric nanocarriers are among one of the effective delivery systems, which has given promising results in the treatment of breast cancers. Nanocarriers does exert their anticancer effect either through active or passive targeting mode.

    RESULTS: The use of nanocarriers has been resolute about the adverse effects of chemotherapeutic drugs such as poor solubility and less penetrability in tumor cells.

    CONCLUSION: The present review is focused on recent developments regarding polymeric nanocarriers, such as polymeric micelles, polymeric nanoparticles, dendrimers, liposomes, nanoshells, fullerenes, carbon nanotubes (CNT) and quantum dots, etc. for their recent advancements in breast cancer therapy.

    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  17. Zhang J, Ming C, Zhang W, Okechukwu PN, Morak-Młodawska B, Pluta K, et al.
    Drug Des Devel Ther, 2017;11:3045-3063.
    PMID: 29123378 DOI: 10.2147/DDDT.S144415
    The asymptomatic properties and high treatment resistance of ovarian cancer result in poor treatment outcomes and high mortality rates. Although the fundamental chemotherapy provides promising anticancer activities, it is associated with severe side effects. The derivative of phenothiazine, namely, 10H-3,6-diazaphenothiazine (PTZ), was synthesized and reported with ideal anticancer effects in a previous paper. In this study, detailed anticancer properties of PTZ was examined on A2780 ovarian cancer cells by investigating the cytotoxicity profiles, mechanism of apoptosis, and cell invasion. Research outcomes revealed PTZ-induced dose-dependent inhibition on A2780 cancer cells (IC50 =0.62 µM), with significant less cytotoxicity toward HEK293 normal kidney cells and H9C2 normal heart cells. Generation of reactive oxygen species (ROS) and polarization of mitochondrial membrane potential (ΔΨm) suggests PTZ-induced cell death through oxidative damage. The RT2 Profiler PCR Array on apoptosis pathway demonstrated PTZ-induced apoptosis via intrinsic (mitochondria-dependent) and extrinsic (cell death receptor-dependent) pathway. Inhibition of NF-κB and subsequent inhibition of (BIRC6-XIAP) complex activities reduced the invasion rate of A2780 cancer cells penetrating through the Matrigel™ Invasion Chamber. Lastly, the cell cycle analysis hypothesizes that the compound is cytostatic and significantly arrests cell proliferation at G2/M phase. Hence, the exploration of the underlying anticancer mechanism of PTZ suggested its usage as promising chemotherapeutic agent.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  18. Barahuie F, Dorniani D, Saifullah B, Gothai S, Hussein MZ, Pandurangan AK, et al.
    Int J Nanomedicine, 2017;12:2361-2372.
    PMID: 28392693 DOI: 10.2147/IJN.S126245
    Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  19. Wong TW, Sriamornsak P, Dass CR
    Curr Drug Deliv, 2018 1 2;14(8):1052.
    PMID: 29290178 DOI: 10.2174/156720181408171213150655
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  20. Ghanghoria R, Kesharwani P, Tekade RK, Jain NK
    J Control Release, 2018 01 10;269:277-301.
    PMID: 27840168 DOI: 10.1016/j.jconrel.2016.11.002
    Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
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