Denver T Hendricks

Guru Nanak Dev University, Amritsar, Punjab, India

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Publications (37)85.5 Total impact

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    ABSTRACT: The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.
    Oncology reports. 06/2014;
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    Katie E Hadley, Denver T Hendricks
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    Katie E Hadley, Denver T Hendricks
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    ABSTRACT: Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status.
    BMC Cancer 05/2014; 14(1):334. · 3.33 Impact Factor
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    ABSTRACT: The anion derived from isatins (I) reacts with isocyanates (II) to form imidazolidine-2-thiones (III), some of which show significant cytotoxic activity against the oesophageal cancer cell line WHCO1.
    ChemInform 02/2014; 45(5).
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    ABSTRACT: Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004.
    South African Journal of Science 01/2014; · 0.84 Impact Factor
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    ABSTRACT: A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodiumfalciparum. The quinoline compounds show enhanced activity compared to the ferrocene compounds against this parasite. Compound 5 displays the most promising activity against the NF54 strain. Compounds 5 and 6 are effective at inhibiting β-hematin formation perhaps due to an increased number of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds also inhibit β-hematin formation, albeit to a lesser degree compared to the quinoline thioureas. The compounds were also screened against the G3 strain of Trichomonasvaginalis and here the ferrocene-containing compounds show a slightly higher parasite growth inhibition compared to the quinoline thioureas. The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells.
    European Journal of Medicinal Chemistry 08/2013; 69C:90-98. · 3.43 Impact Factor
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    ABSTRACT: Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC(50) 1.6-11.7 μM) compared to the current drug of choice cisplatin (IC(50) = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC(50) = 3.0 and 7.3 μM) and the previously reported compound 11a (IC(50) = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.
    European Journal of Medicinal Chemistry 01/2013; 62C:98-110. · 3.43 Impact Factor
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    ABSTRACT: Two silicon-containing analogues (1, 2) of chloroquine, modified in the lateral side chain with organosilicon moieties, were synthesized. Compounds 1 and 2 were further reacted with dinuclear half-sandwich transition metal precursors [Ru(Ar)(μ-Cl)Cl] 2 (Ar = η 6 -p-i PrC 6 H 4 Me; η 6 -C 6 H 6 ; η 6 -C 6 H 5 OCH 2 CH 2 OH), [Rh(COD)(μ-Cl)] 2 , and [RhCp*(μ-Cl)Cl] 2 , to yield a series of neutral mononuclear Ru(II), Rh(I), and Rh(III) silicon-aminoquinoline complexes (3−12). Compounds 1 and 2 act as monodentate donors that coordinate to the transition metals via the quinoline nitrogen of the aminoquinoline scaffold. All the compounds were characterized using various analytical and spectroscopic techniques, and the molecular structures of compounds 2 and 11 were elucidated by single-crystal X-ray diffraction analysis. Furthermore, the in vitro pharmacological activities of compounds 1−12 were established against chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the malarial parasite Plasmodium falciparum and against the pathogenic bacterium Mycobacterium tuberculosis H 37 R v , as well as an esophageal (WHCO1) cancer cell line.
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    ABSTRACT: N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction. Although no measurable effects on in vitro cell proliferation were observed with altered NDRG1 expression, the ectopic overexpression of NDRG1 was positively linked to recognized markers of metastasis, angiogenesis and apoptotic evasion. Accordingly, in the nude mouse xenograft model system, NDRG1 overexpression promoted the in vivo growth of KYSE30 derived xenografts, which could be attributed to the reduced apoptotic and enhanced angiogenic activities associated with this gene. These processes were mediated in part by increased NFκB activity in NDRG1 overexpressing cells. Nevertheless, no significant phenotypic changes were observed in response to NDRG1 knock-down, suggesting that this gene might not be essential for the neoplastic progression of ESCC. Taken together, our results suggest that NDRG1 may play positive but dispensable roles in the progression of esophageal squamous cell carcinoma.
    Cancer biology & therapy 11/2012; 14(2). · 3.29 Impact Factor
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    ABSTRACT: A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized β-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97μM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates.
    European Journal of Medicinal Chemistry 11/2012; 58C:513-518. · 3.43 Impact Factor
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    ABSTRACT: The title compound C(18)H(16)N(2)S(2), crystallizes with two independent half-mol-ecules in the asymmetric unit, in one of which the thio-phene rings are disordered in a 0.67:0.33 ratio. Each independent mol-ecule lies across a crystallographic centre of symmetry. The dihedral angle between central (half) benzene ring and the thiophene ring is 11.82°.
    Acta Crystallographica Section E Structure Reports Online 11/2012; 68(Pt 11):o3137. · 0.35 Impact Factor
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    ABSTRACT: a b s t r a c t The reactions of iminophosphine ligands with [PtCl 2 (COD)], [PtCl 2 (DMSO) 2 ], and [Au(tht)Cl] has been inves-tigated. The new platinum(II) and gold(I) complexes were characterised using elemental analysis, electro-spray ionisation-mass spectrometry (ESI-MS), NMR (1 H and 31 P) and IR spectroscopy and X-ray diffraction studies. In vitro cytotoxic study results show that platinum and gold complexes block the proliferation of WHCO1 and KYSE450 cell lines with an IC 50 range of 2.16–9.47 lM.
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    ABSTRACT: To determine the association between serum levels of growth-related gene product β (GROβ) and clinical parameters in esophageal squamous cell carcinoma (ESCC). Using enzyme-linked immunosorbent assay, serum GROβ levels were measured in ESCC patients (n = 72) and healthy volunteers (n = 83). The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically. The serum GROβ levels were much higher in ESCC patients than in healthy controls (median: 645 ng/L vs 269 ng/L, P < 0.05). Serum GROβ levels were correlated positively with tumor size, lymph node metastasis, and tumor-node-metastasis (TNM) staging, but not with gender or the histological grade of tumors in ESCC patients. The sensitivity and specificity of the assay for serum GROβ were 73.61% and 56.63%, respectively. GROβ may function as an oncogene product and contribute to tumorigenesis and metastasis of ESCC.
    World Journal of Gastroenterology 06/2011; 17(21):2658-62. · 2.55 Impact Factor
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    ABSTRACT: In the title compound, C(22)H(22)N(4), the centroid of the benzene ring is located on an inversion centre. The dihedral angle between the benzene and pyridine rings is 10.94 (5)°. The crystal structure displays weak inter-molecular C-H⋯N hydrogen bonding and C-H⋯π inter-actions.
    Acta Crystallographica Section E Structure Reports Online 04/2011; 67(Pt 4):o921. · 0.35 Impact Factor
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    ABSTRACT: Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R∗,4S∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R∗,4S∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1). Compounds 1-6 showed greater cytotoxicity in this assay as compared to the known anticancer drug cisplatin.
    Phytochemistry 03/2011; 72(8):769-72. · 3.35 Impact Factor
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    ABSTRACT: A series of mono- and dinuclear (η6-arene) ruthenium(II) complexes were prepared by reaction of thiosemicarbazone ligands derived from benzaldehyde and ruthenium(II) precursors of the general formula [Ru(η6-arene)(μ-Cl)Cl]2, where arene=p-iPrC6H4Me or C6H5C3H6COOH. These complexes were characterized by NMR and IR spectroscopy, ESI-mass spectrometry and elemental analysis. The molecular structure of the mononuclear p-cymene complex was determined by X-ray diffraction analysis, revealing a pseudo-tetrahedral piano stool conformation and a bidentate N,S coordination mode of the thiosemicarbazone ligand. The complexes and ligands were evaluated for their in vitro cytotoxicity against the WHCO1 oesophageal cancer cell line.
    Inorganic Chemistry Communications - INORG CHEM COMMUN. 01/2011; 14(6):956-960.
  • Qiaomei Dong, Jinqiang Zhang, Denver T Hendricks, Xiaohang Zhao
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    ABSTRACT: Cisplatin is one of the most widely used chemotherapeutic agents employed for treatment of a wide variety of solid tumors, including human esophageal squamous cell carcinoma (ESCC). However, a major limitation of cisplatin-based chemotherapy of ESCC is the rather low-effective rate. Understanding the molecular events of limited efficacy of cisplatin-based chemotherapy of ESCC could lead to strategies resulting in improved therapeutic benefits. The CXC chemokine family has been reported to be related to inflammatory reaction, injure recovery, cell proliferation, apoptosis and even to be involved in the regulation of chemotherapeutic agent-induced apoptosis. CXCL2 chemokine, also known as GROβ (growth-related gene product β), belongs to the CXC chemokine group. The known functions of GROβ are related to attracting neutrophils to sites of inflammation, modulation of the neurotransmitter release, cell proliferation and apoptosis. However, little is known about the relationship between GROβ and chemotherapeutic agent-induced apoptosis. This study was designed to provide insights into the possible role of GROβ in the regulation of cisplatin-induced apoptosis in ESCCs. We report here that inhibition of expression of GROβ can decrease cisplatin-induced apoptosis in WHCO1 cells. EGR1 is a downstream factor regulated by GROβ. Silencing expression of EGR1 can also decrease cisplatin-induced apoptosis in WHCO1 cells. The activation of caspase 9 was delayed in cells in which GROβ and EGR1 were knocked down after cisplatin treatment. All these results indicate that GROβ and its downstream factor EGR1 are involved in regulating cisplatin-induced apoptosis in WHCO1 cells, and during this process the intrinsic apoptotic pathway is activated. It may be useful to examine the expression levels of GROβ and EGR1 in ESCC patients to select those likely to respond well to cisplatin.
    Oncology Reports 01/2011; 25(4):1031-7. · 2.30 Impact Factor
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    ABSTRACT: a b s t r a c t A series of di-and trithiosemicarbazone ligands as well as their Pd(II) and Pt(II) 1,3,5-triaza-7-phospha-adamantane (PTA) complexes have been synthesised using templated reactions between various substi-tuted salicylaldimine thiosemicarbazone ligands and metal precursors of the general formula cis-[M(PTA) 2 Cl 2 ], where M = Pd or Pt. Characterization of these complexes was achieved using various ana-lytical and spectroscopic techniques: elemental analysis, ESI-MS, FT-IR, and NMR (1 H, 13 C{ 1 H} and 31 P{ 1 H}) spectroscopy. The data revealed tridentate (O–N–S) coordination of the thiosemicarbazone moi-eties via the imine nitrogen, thiolato sulfur and phenolic oxygen to each metal center. In vitro biological evaluation of selected compounds was conducted against WHCO1 oesophageal cancer cells. Some of the multimeric compounds display some promising biological activity.
    Polyhedron. 01/2011;
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    ABSTRACT: A series of mononuclear salicylaldiminato(thiosemicarbazone)palladium(II) complexes of general formula [Pd(saltsc-R)PPh3], {H2saltsc-R = salicylaldehyde thiosemicarbazone; R = H (5), 3-tert-butyl (6), 3-methoxy (7), 5-chloro (8)} have been synthesized. The palladium complexes were prepared by the reaction of the appropriate salicylaldimine thiosemicarbazone with Pd(PPh3)2Cl2. All complexes were characterised by a range of spectroscopic and analytical techniques. The molecular structures of 6–8 have been determined by single-crystal X-ray diffraction analysis. The salicylaldimine thiosemicarbazones coordinate to palladium in a tridentate manner, through the phenolic oxygen, imine nitrogen and thiolate sulfur, forming five-and six-membered chelate rings within their structures. The fourth coordination site for these square-planar complexes is occupied by PPh3. Biological activities of the thiosemicarbazone ligands and palladium complexes have been investigated toward the WHCO1 oesophageal cancer cell line and against two strains of the malaria parasite Plasmodium falciparum, W2 (chloroquine-resistant) and D10 (chloroquine-sensitive). The palladium(II) complexes show enhanced in vitro antiplasmodial activity in comparison with their thiosemicarbazone ligand precursors. On the other hand, in vitro anticancer activity studies on oesophageal cancer cell lines revealed a decrease in activity upon coordination of palladium to the thiosemicarbazone ligand.
    Berichte der deutschen chemischen Gesellschaft 06/2010; 2010(22):3520 - 3528. · 2.94 Impact Factor
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    ABSTRACT: Although early growth response-1 (EGR-1) has been shown as a key transcription factor in controlling cell growth, proliferation, differentiation, and angiogenesis, its role in the development of esophageal cancer is poorly understood despite the high frequency of this disease in many parts of the world. Here, immunohistochemistry showed that EGR-1 is overexpressed in 80% of esophageal tumor tissues examined. Furthermore, EGR-1 is constitutively expressed in all esophageal cancer cell lines analyzed. Esophageal squamous carcinoma WHCO1 cells stably transfected with EGR-1 short hairpin RNA displayed a 55% reduction in EGR-1 protein levels, 50% reduction in cell proliferation, a 50% reduction in cyclin-dependent kinase 4 levels, and a 2-fold induction in p27(Kip1) levels associated with a G(2)-M cell cycle arrest. EGR-1 knockdown also caused a marked induction in IkappaBalpha expression, an effect also observed in GRObeta RNA interference-expressing WHCO1 cells, because EGR-1 lies downstream of GRO/CXCR2 signaling. Furthermore, p65 mRNA levels were also reduced in cells treated with either short hairpin RNA EGR-1 or small interfering RNA EGR-1. Immunohistochemical analysis indicated that p65 is elevated in 78% (n = 61) of esophageal tumor sections analyzed. Moreover, nuclear factor-kappaB inhibition with either sodium salicylate or p65 RNA interference led to a significant reduction in GROalpha and GRObeta expression. These results indicate that EGR-1 and nuclear factor-kappaB mediate GRO/CXCR2 proliferative signaling in esophageal cancer and may represent potential target molecules for therapeutic intervention.
    Molecular Cancer Research 06/2009; 7(5):755-64. · 4.35 Impact Factor

Publication Stats

285 Citations
85.50 Total Impact Points

Institutions

  • 2014
    • Guru Nanak Dev University
      • Department of Chemistry
      Amritsar, Punjab, India
  • 2002–2014
    • University of Cape Town
      • • Division of Medical Biochemistry
      • • Department of Chemistry
      • • Institute of Infectious Disease & Molecular Medicine (IIDMM)
      • • Faculty of Health Sciences
      Kaapstad, Western Cape, South Africa
  • 2005–2013
    • Rhodes University
      • • Department of Chemistry
      • • Faculty of Pharmacy
      Grahamstown, Province of Eastern Cape, South Africa