Displaying all 7 publications

Abstract:
Sort:
  1. Tan ML, Ooi JP, Ismail N, Moad AI, Muhammad TS
    Pharm Res, 2009 Jul;26(7):1547-60.
    PMID: 19407932 DOI: 10.1007/s11095-009-9895-1
    Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.
    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology*
  2. Mozar FS, Chowdhury EH
    Curr Drug Deliv, 2015;12(3):333-41.
    PMID: 25600981
    Substantial amount of research has been done in recent decades for the development of nanoparticle systems to selectively deliver drugs to cancer cells for concurrently enhancing and reducing anti-cancer and off-target effects, respectively. pH-sensitive carbonate apatite (CA) was originally developed for efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell lines. Recently, the CA particles were employed to deliver anti-cancer drugs, cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report on the fabrication and characterization of gemcitabine- loaded CA particles, followed by the evaluation of their roles in enhancement of cytotoxicity in two human and one murine breast cancer cell lines. HPLC was performed to measure binding efficiency of the drug to the apatite particles whereas particle size and zeta potential were evaluated to characterize drug/apatite complex. Depending on the initial doses of the drug, its bind binding affinity towards the particles varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease with an increase of the initial drug concentration. In vitro chemosensitivity assay revealed that apatite/drug nanoparticle complexes presented significantly higher cytotoxicity to breast cancer cells compared to free drugs, which could be correlated with the enhanced cellular uptake of the small size drug-loaded particles through endocytosis compared to the passive diffusion of the free drug.
    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
  3. 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: Antimetabolites, Antineoplastic/pharmacology
  4. Ebadi M, Buskaran K, Saifullah B, Fakurazi S, Hussein MZ
    Int J Mol Sci, 2019 Aug 01;20(15).
    PMID: 31374834 DOI: 10.3390/ijms20153764
    One of the current developments in drug research is the controlled release formulation of drugs, which can be released in a controlled manner at a specific target in the body. Due to the diverse physical and chemical properties of various drugs, a smart drug delivery system is highly sought after. The present study aimed to develop a novel drug delivery system using magnetite nanoparticles as the core and coated with polyvinyl alcohol (PVA), a drug 5-fluorouracil (5FU) and Mg-Al-layered double hydroxide (MLDH) for the formation of FPVA-FU-MLDH nanoparticles. The existence of the coated nanoparticles was supported by various physico-chemical analyses. In addition, the drug content, kinetics, and mechanism of drug release also were studied. 5-fluorouracil (5FU) was found to be released in a controlled manner from the nanoparticles at pH = 4.8 (representing the cancerous cellular environment) and pH = 7.4 (representing the blood environment), governed by pseudo-second-order kinetics. The cytotoxicity study revealed that the anticancer delivery system of FPVA-FU-MLDH nanoparticles showed much better anticancer activity than the free drug, 5FU, against liver cancer and HepG2 cells, and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.
    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
  5. Soni N, Soni N, Pandey H, Maheshwari R, Kesharwani P, Tekade RK
    J Colloid Interface Sci, 2016 Nov 01;481:107-16.
    PMID: 27459173 DOI: 10.1016/j.jcis.2016.07.020
    Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety.
    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
  6. Nasir SN, Abu N, Ab Mutalib NS, Ishak M, Sagap I, Mazlan L, et al.
    Clin Transl Oncol, 2018 Jun;20(6):775-784.
    PMID: 29098557 DOI: 10.1007/s12094-017-1788-x
    PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

    METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

    RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

    CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
  7. Yusefi M, Shameli K, Jahangirian H, Teow SY, Umakoshi H, Saleh B, et al.
    Int J Nanomedicine, 2020;15:5417-5432.
    PMID: 32801697 DOI: 10.2147/IJN.S250047
    INTRODUCTION: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy.

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

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

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

    Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links