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  1. Fulltext In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica
    Malami I, Abdul AB, Abdullah R, Bt Kassim NK, Waziri P, Christopher Etti I
    Molecules, 2016 Apr 08;21(4):417.
    PMID: 27070566 DOI: 10.3390/molecules21040417
    Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development.
    Matched MeSH terms: Antineoplastic Agents/therapeutic use; Antineoplastic Agents/chemistry
  2. Reprogramming cancer cells: overview & current progress
    Lim KL, Teoh HK, Choong PF, Teh HX, Cheong SK, Kamarul T
    Expert Opin Biol Ther, 2016 07;16(7):941-51.
    PMID: 27070264 DOI: 10.1517/14712598.2016.1174211
    INTRODUCTION: Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model.

    AREAS COVERED: Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents.

    EXPERT OPINION: Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

    Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use
  3. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds
    Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, et al.
    Semin Cancer Biol, 2016 10;40-41:35-47.
    PMID: 27038646 DOI: 10.1016/j.semcancer.2016.03.005
    The association between chronic inflammation and cancer development has been well documented. One of the major obstacles in cancer treatment is the persistent autocrine and paracrine activation of pro-inflammatory transcription factors such as nuclear factor-κB, signal transducer and activator of transcription 3, activator protein 1, fork head box protein M1, and hypoxia-inducible factor 1α in a wide variety of tumor cell lines and patient specimens. This, in turn, leads to an accelerated production of cellular adhesion molecules, inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible nitric oxide synthase. Numerous medicinal plant-derived compounds have made a tremendous impact in drug discovery research endeavors, and have been reported to modulate the activation of diverse oncogenic transcription factors in various tumor models. Moreover, novel therapeutic combinations of standard chemotherapeutic drugs with these agents have significantly improved patient survival by making cancer cells more susceptible to chemotherapy and radiotherapy. In this review, we critically analyze the existing literature on the modulation of diverse transcription factors by various natural compounds and provide views on new directions for accelerating the discovery of novel drug candidates derived from Mother Nature.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/therapeutic use
  4. 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: Antineoplastic Agents, Phytogenic/administration & dosage*; Antineoplastic Agents, Phytogenic/chemistry
  5. Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting neuropilin-1 for anticancer application
    Kamarulzaman EE, Vanderesse R, Gazzali AM, Barberi-Heyob M, Boura C, Frochot C, et al.
    J Biomol Struct Dyn, 2017 Jan;35(1):26-45.
    PMID: 26766582 DOI: 10.1080/07391102.2015.1131196
    Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) are important targets of many pro-angiogenic factors. In this study, nine peptides were synthesized and evaluated for their molecular interaction with NRP-1 and compared to our previous peptide ATWLPPR. Docking study showed that the investigated peptides shared the same binding region as shown by tuftsin known to bind selectively to NRP-1. Four pentapeptides (DKPPR, DKPRR, TKPPR and TKPRR) and a hexapeptide CDKPRR demonstrated good inhibitory activity against NRP-1. In contrast, peptides having arginine residue at sites other than the C-terminus exhibited low activity towards NRP-1 and this is confirmed by their inability to displace the VEGF165 binding to NRP-1. Docking study also revealed that replacement of carboxyl to amide group at the C-terminal arginine of the peptide did not affect significantly the binding interaction to NRP-1. However, the molecular affinity study showed that these peptides have marked reduction in the activity against NRP-1. Pentapeptides having C-terminal arginine showed strong interaction and good inhibitory activity with NRP thus may be a good template for anti-angiogenic targeting agent.
    Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry*
  6. Symptom Prevalence and Related Distress in Cancer Patients Undergoing Chemotherapy
    Thiagarajan M, Chan CM, Fuang HG, Beng TS, Atiliyana MA, Yahaya NA
    Asian Pac J Cancer Prev, 2016;17(1):171-6.
    PMID: 26838205
    BACKGROUND: Much has been done to examine the psychological impact of cancer treatment, but it remains unclear to what extent anxiety and depression is related to symptom prevalence. The present study concerned the characteristics and frequency of distress as related to symptom prevalence in cancer patients undergoing chemotherapy in Malaysia.

    MATERIALS AND METHODS: Participants were 303 consecutive adult cancer patients undergoing chemotherapy in an academic medical center. The short form Memorial Symptom Assessment Scale (MSAS-SF), which covers three domains of symptoms (global distress, physical- and psychological symptoms) was used to cross-sectionally measure symptom frequency and associated distress via self-reporting. One-way ANOVA and t-tests were used to test mean differences among MSAS-SF subscale scores.

    RESULTS: Complete data were available for 303 patients. The mean number of symptoms was 14.5. The five most prevalent were fatigue, dry mouth, hair loss, drowsiness and lack of appetite. Overall, symptom burden and frequency were higher than in other published MSAS-SF studies. Higher symptom frequency was also found to be significantly related to greater distress in cancer patients undergoing chemotherapy.

    CONCLUSIONS: Patients undergoing chemotherapy suffer from multiple physical and psychological symptoms. Better symptom control or palliative care is needed. Greater frequency of reported symptoms may also indicate a subconscious bid by patients for care and reassurance - thus tailored intervention to manage distress should be offered.

    Matched MeSH terms: Antineoplastic Agents/adverse effects*; Antineoplastic Agents/therapeutic use
  7. A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells
    Viswanathan G, Hsu YH, Voon SH, Imae T, Siriviriyanun A, Lee HB, et al.
    Macromol Biosci, 2016 06;16(6):882-95.
    PMID: 26900760 DOI: 10.1002/mabi.201500435
    Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage; Antineoplastic Agents/chemistry
  8. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer: A historical cohort study
    Bhoo-Pathy N, Verkooijen HM, Wong FY, Pignol JP, Kwong A, Tan EY, et al.
    Int J Cancer, 2015 Nov 15;137(10):2504-12.
    PMID: 26018878 DOI: 10.1002/ijc.29617
    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. Survival between patients receiving mastectomy only, breast-conserving therapy (BCT, lumpectomy and adjuvant radiotherapy) and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics and chemotherapy types. Median age at diagnosis was 53 years (range: 23-96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node-negative disease. The majority of patients received adjuvant chemotherapy (n = 861, 76%) comprising predominantly anthracycline-based regimes. In 775 women with T1-2, N0-1, M0 TNBCs, 5-year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95% CI: 88.8-98.8%), followed by BCT (90.8%, 95% CI: 85.0-94.7%), and mastectomy with radiotherapy (82.3%, 95% CI: 73.4-88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3-4, N2-3, M0 TNBCs, BCT was associated with highest 5-year RSR (94.1%, 95% CI: 81.3-99.4%), followed by mastectomy with radiotherapy (62.7%, 95% CI: 54.3-70.1%), and mastectomy only (58.6%, 95% CI: 43.5-71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/therapeutic use
  9. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery
    Ma Y, Fuchs AV, Boase NR, Rolfe BE, Coombes AG, Thurecht KJ
    Eur J Pharm Biopharm, 2015 Aug;94:393-403.
    PMID: 26117186 DOI: 10.1016/j.ejpb.2015.06.014
    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/pharmacokinetics
  10. Berberis vulgaris fruit crude extract as a novel anti-leukaemic agent
    Saedi TA, Ghafourian S, Jafarlou M, Sabariah MN, Ismail P, Eusni RM, et al.
    J Biol Regul Homeost Agents, 2015 Apr-Jun;29(2):395-9.
    PMID: 26122228
    Tumor protein p53 encoded by the TP53 gene in humans is known as a cancer biomarker in patients diagnosed with cancer, and it plays an essential role in apoptosis, genomic stability, and inhibition of angiogenesis. Cancer therapies with common chemotherapy methods are effective, as known, but have some side effects. Berberis vulgaris is traditionally administrated as a cancer drug. The current research aims to evaluate p53 as a biomarker in WEHI-3 cell line and to demonstrate the Berberis vulgaris fruit crude extract (BVFCE) as a new anticancer drug. For this purpose, we evaluated the effect of BVFCE in different concentrations against WEHI-3cell line in vitro and determined the quantitative level of p53 gene in the treated WEHI-3 cells. The results demonstrated that even at only 1 mg/ml concentration of Berberis vulgaris crude extract, there was a low level of p53 biomarker expression on WEHI-3 cells in comparison with doxorubicin. Therefore, the current study suggests BVFCE as a reliable anti-leukaemic drug and candidate for anticancer therapy. However, further investigation need be carried out to confirm its efficiency in vivo.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/pharmacology*
  11. Fulltext Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract
    Abdullah AS, Mohammed AS, Rasedee A, Mirghani ME, Al-Qubaisi MS
    BMC Complement Altern Med, 2015;15:45.
    PMID: 25881293 DOI: 10.1186/s12906-015-0575-x
    In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/therapeutic use
  12. Polymer-albumin conjugate for the facilitated delivery of macromolecular platinum drugs
    Dag A, Jiang Y, Karim KJ, Hart-Smith G, Scarano W, Stenzel MH
    Macromol Rapid Commun, 2015 May;36(10):890-7.
    PMID: 25790077 DOI: 10.1002/marc.201400576
    The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N-(2-hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3-diaminopropan-2-yl acrylate (Ac-DAP-Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition-fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14 -co-(Ac-DAP-Boc)9 ) and a molecular weight of Mn = 7600 g mol(-1) (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI-TOF (matrix assisted laser desorption ionization time-of-flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer-albumin conjugates self-assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry
  13. Tocotrienols inhibit growth of ZR-75-1 breast cancer cells
    Nesaretnam K, Dorasamy S, Darbre PD
    Int J Food Sci Nutr, 2000;51 Suppl:S95-103.
    PMID: 11271861
    The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/therapeutic use*
  14. Fulltext Tretinoin in pregnancy complicated with acute promyelocytic leukaemia
    Leong KW, Teh A, Bosco JJ
    Med J Malaysia, 2000 Jun;55(2):277-9.
    PMID: 19839162
    Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.
    Matched MeSH terms: Antineoplastic Agents/adverse effects; Antineoplastic Agents/therapeutic use*
  15. Flavonol-cinnamate cycloadducts and diamide derivatives from Aglaia laxiflora
    Xu YJ, Wu XH, Tan BK, Lai YH, Vittal JJ, Imiyabir Z, et al.
    J Nat Prod, 2000 Apr;63(4):473-6.
    PMID: 10785416
    Leaf extracts of the Malaysian plant Aglaia laxiflora provided two cytotoxic compounds, a new rocaglaol rhamnoside (1), a known rocaglaol (2), new (but inactive) flavonol-cinnamaminopyrrolidine adducts (3-6), and their probable biosynthetic precursors (7 and trimethoxyflavonol). All structures were elucidated primarily by 2D NMR spectroscopy. The structure and stereochemistry of aglaxiflorin A (3) were confirmed by single-crystal X-ray crystallography.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*; Antineoplastic Agents, Phytogenic/pharmacology
  16. Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study
    Prasad U, bin Jalaludin MA, Rajadurai P, Pizza G, De Vinci C, Viza D, et al.
    Biotherapy, 1996;9(1-3):109-15.
    PMID: 8993768
    Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P = < 0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.
    Matched MeSH terms: Antineoplastic Agents/immunology; Antineoplastic Agents/therapeutic use*
  17. Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii
    Kam TS, Sim KM, Koyano T, Toyoshima M, Hayashi M, Komiyama K
    J Nat Prod, 1998 Nov;61(11):1332-6.
    PMID: 9834146
    The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/pharmacology*
  18. 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: Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry*
  19. Fulltext Establishment of in vitro and in vivo anti-colon cancer efficacy of essential oils containing oleo-gum resin extract of Mesua ferrea
    Asif M, Yehya AHS, Dahham SS, Mohamed SK, Shafaei A, Ezzat MO, et al.
    Biomed Pharmacother, 2019 Jan;109:1620-1629.
    PMID: 30551416 DOI: 10.1016/j.biopha.2018.10.127
    Proven the great potential of essential oils as anticancer agents, the current study intended to explore molecular mechanisms responsible for in vitro and in vivo anti-colon cancer efficacy of essential oil containing oleo-gum resin extract (RH) of Mesua ferrea. MTT cell viability studies showed that RH had broad spectrum cytotoxic activities. However, it induced more profound growth inhibitory effects towards two human colon cancer cell lines i.e., HCT 116 and LIM1215 with an IC50 values of 17.38 ± 0.92 and 18.86 ± 0.80 μg/mL respectively. RH induced relatively less toxicity in normal human colon fibroblasts i.e., CCD-18co. Cell death studies conducted, revealed that RH induced characteristic morphological and biochemical changes in HCT 116. At protein level it down-regulated expression of multiple pro-survival proteins i.e., survivin, xIAP, HSP27, HSP60 and HSP70 and up-regulated expression of ROS, caspase-3/7 and TRAIL-R2 in HCT 116. Furthermore, significant reduction in invasion, migration and colony formation potential was observed in HCT 116 treated with RH. Chemical characterization by GC-MS and HPLC methods revealed isoledene and elemene as one the major compounds. RH showed potent antitumor activity in xenograft model. Overall, these findings suggest that RH holds a promise to be further studied for cheap anti-colon cancer naturaceutical development.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/therapeutic use*
  20. Purification, characterization and utilization of polysaccharide of Araucaria heterophylla gum for the synthesis of curcumin loaded nanocarrier
    Samrot AV, Angalene JLA, Roshini SM, Stefi SM, Preethi R, Raji P, et al.
    Int J Biol Macromol, 2019 Nov 01;140:393-400.
    PMID: 31425761 DOI: 10.1016/j.ijbiomac.2019.08.121
    In this study, gum of Araucaria heterophylla was collected. The collected gum was subjected for extraction of polysaccharide using solvent extraction system. Thus, extracted polysaccharide was further purified using solvent method and was characterized using UV-Vis spectroscopy, Phenol sulfuric acid assay, FTIR, TGA, TLC and GC-MS. The gum derived polysaccharide was found to have the following sugars Rhamnose, Allose, Glucosinolate, Threose, Idosan, Galactose and Arabinose. The extracted polysaccharide was tested for various in-vitro bioactive studies such as antibacterial activity, antioxidant activity and anticancer activity. The polysaccharide was found to have antioxidant and anticancer activity. Further, the polysaccharide was subjected for carboxymethylation to favor the nanocarrier synthesis, where it was chelated using Sodium Tri Meta Phosphate (STMP) to form nanocarriers. The nanocarriers so formed were loaded with curcumin and were characterized using FTIR, SEM, EDX and AFM. Both the loaded and unloaded nanocarriers were studied for its in-vitro cytotoxic effect against the MCF7 human breast cancer cell lines. The nanocarriers were found to deliver the drug efficiently against the cancer cell line used in this study.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry
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