Research interests

This research group has two main areas of interest:

1) Determine the molecular mechanisms involved in the development and maintenance of oesophageal cancer.
Although squamous cell carcinoma of the oesophagus occurs with a high frequency in South Africa, the molecular mechanisms involved in the development and maintenance of this disease is still poorly understood. We have recently demonstrated the presence of a functional GRO/CXCR2 autocrine loop in oesophageal cancer cells that contribute to cancer cell survival and proliferation (5). Blocking this chemokine autocrine loop significantly reduces the proliferation of oesophageal cancer cells. We are presently exploring the signalling events associated with this chemokine loop in more detail, and also the relationship between the CXCR2 receptor system and other proliferative pathways in oesophageal cancer cells. We are also investigating the role of NDRG-1 (nMyc downstream regulated gene 1) in oesophageal cancer since there is conflicting evidence regarding the involvement of this gene in cancer cell proliferation and metastasis. These genes are currently being further explored to determine their role in the development of oesophageal cancer, and their utility as early markers, therapeutic targets, or prognostic indicators.

2) The identification and characterisation of novel compounds that can be used in the treatment of cancer.
Since we have a very high incidence of oesophageal cancer in South Africa, and given that this disease is associated with a high mortality rate, we are presently testing potential therapeutic leads in cultured oesophageal cancer cells as a model system. This may allow us to identify agents that are chemotherapeutically active in these diseases that have high mortality rates in South Africa.

We are currently examining, i) laboratory synthesized chemical compounds and ii) indigenous natural products as sources for potential chemotherapeutic agents. Southern Africa has a very high diversity of endemic flora and marine organisms that could potentially yield lead agents that could be used in the development of chemotherapeutic agents for the treatment of cancer. Together with our collaborators (Prof. Mike Coleman-Davies, an organic chemist from Rhodes University, and systematists from other institutions), we are currently screening marine organisms (ascidians, soft coral and sponges) collected from southern African coastal waters. We have shown that these organisms do indeed contain novel organic compounds, and that some of these display anti-cancer activity (see 1b, 2, 3, 4 and 6) Some of these compounds are being explored further to elucidate their mechanism of action (for further development) and so that potential targets for future drug development can be identified. Our approach includes measuring the effects of these agents on cell growth, quantitating the extent of apoptosis, and characterising the pathways activated in the apoptotic cascade. We also collaborate with organic chemists at UCT (Prof. John Moss) to determine if we can develop novel compounds that are more effective than the commonly used chemotherapeutic agent, cisplatin.

Group Members

Publications 2003-2010

1. Chellan P, Shunmoogam-Gounden N, Hendricks DT, Gut J, Rosenthal PJ, Lategan C, Smith PJ, Chibale K, Smith GS. 
   Synthesis, Structure and in Vitro Biological Screening of Palladium(II) Complexes of Functionalised Salicylaldimine Thiosemicarbazones as Antimalarial and Anticancer Agents. 
   European Journal of Inorganic Chemistry, 2010, 3520-3528. 
    
2. Van Der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender  D, Birrer MJ, Leaner VD.
   The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
   International Journal of Cancer, 2009, 124: 1829-1840
    
3. Stringer T, Chellan P, Therrien B, Shunmoogam-Gounden N, Hendricks DT, Smith GS.
   Synthesis and structural characterization of binuclear palladium(II) complexes of salicylaldimine dithiosemicarbazones
   Polyhedron, 2009, 28: 2839-2846
    
4. Van der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender D, Birrer MJ, Leaner VD.
   The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
   Int J Cancer. 2008 Nov 11. [Epub ahead of print]
    
5. van Wyk AW, Gray CA, Whibley CE, Osoniyi O, Hendricks DT, Caira MR, Davies-Coleman MT.
   Bioactive metabolites from the South African marine mollusk Trimusculus costatus.
   J Nat Prod. 2008 Mar;71(3):420-5. Epub 2008 Feb 21.Matsha T, Donninger H, Erasmus RT, Hendricks D, Stepien A, Parker MI. (2007). Expression of p53 and its homolog, p73, in HPV DNA positive oesophageal squamous cell carcinomas. Virology. 2007 Dec 5;369(1):182-90.
    
6. Catherine E Whibley, Kerry L McPhaiul, Robert A Keyzers, Michelle F Maritz, Virna D Leaner, Michael J Birrer, Michael T Davies-Coleman and Denver T Hendricks. (2007). Reactive oxygen species mediated apoptosis of esophageal cancer cells induced by marine triprenyl toluquinones and toluhydroquinones. Mol Cancer Ther. 6 (9): 2535-43.
    
7. Mann MG, Mkwananzi HB, Antunes EM, Whibley CE, Hendricks DT, Bolton JJ, Beukes DR.. (2007). Halogenated monoterpene aldehydes from the South African marine alga Plocamium corallorhiza. J Nat Prod. 2007 Apr;70(4):596-9.
    
8. Keyzers,R.A., Gray,C.A., Schleyer,M.H., Whibley,C.E., Hendricks,D.T., and Davies-Coleman,M.T. (2006). Malonganenones A-C, novel tetraprenylated alkaloids from the Mozambique gorgonian Leptogorgia gilchristi. Tetrahedron 62, 2200-2206.
    
9. Wang,B., Hendricks,D.T., Wamunyokoli,F., and Parker,M.I. (2006). A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 66, 3071-3077.
    
10. Keyzers,R.A., Arendse,C.E., Hendricks,D.T., Samaai,T., and Davies-Coleman,M.T. (2005). Makaluvic acids from the South African latrunculid sponge Strongylodesma aliwaliensis. J. Nat. Prod. 68, 506-510.
     
11. Knott,M.G., Mkwananzi,H., Arendse,C.E., Hendricks,D.T., Bolton,J.J., and Beukes,D.R. (2005). Plocoralides A-C, polyhalogenated monoterpenes from the marine alga Plocamium corallorhiza. Phytochemistry 66, 1108-1112.
     
12. Michael T.Davies-Coleman, William Froneman, Robert A. Keyzers, Catherine Whibley, Denver Hendricks, Toufiek Samaai and Christopher McQuaid. (2005). Anti-oesophageal cancer activity in extracts of deep-water Marion Island sponges. S A J Science 101[November/December], 489-490.
     
13. Rajput,J., Moss,J.R., Hutton,A.T., Hendricks,D.T., Arendse,C.E., and Imrie,C. (2004). Synthesis, characterization and cytotoxicity of some palladium(II), platinum(II), rhodium(I) and iridium(I) complexes of ferrocenylpyridine and related ligands. Crystal and molecular structure of trans-dichlorobis(3-ferrocenylpyridine)palladium(II). Journal of Organometallic Chemistry 689, 1553-1568.
     
14. Davies-Coleman,M.T., Dzeha,T.M., Gray,C.A., Hess,S., Pannell,L.K., Hendricks,D.T., and Arendse,C.E. (2003). Isolation of homodolastatin 16, a new cyclic depsipeptide from a Kenyan collection of Lyngbya majuscula. J. Nat. Prod. 66, 712-715.

Peer-reviewed Conference Proceedings:

1b. Whibley,C.E., Keyzers,R.A., Soper,A.G., Davies-Coleman,M.T., Samaai,T., and Hendricks,D.T. (2005). Antiesophageal cancer activity from southern african marine organisms.   Ann. N. Y. Acad. Sci. 1056, 405-412.

List of Collaborators