Page 74 - University of Pretoria RESEARCH REVIEW 2018
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Targeted drugs for fighting cancer Annie Joubert, Department of Physiology
Globally, cancer is one of the leading causes of mortality. The incidence of cancer is expected to increase as populations age, and as people become more sedentary and adopt lifestyle behaviours that pose as risk factors in cancer development.
particular, ESE-16 has been shown
to limit proliferation by disrupting
the formation of microtubules during cellular replication, eventually causing cell death. This novel compound disrupts the proliferation of breast cancer and cervical cancer cell lines in vitro. Working with colleagues from the Department of Pharmacology at UP and the Biomedical Research Centre at Onderstepoort, the team has
tested the oral bioavailability of these compounds in mice and found that three ESE derivatives were still present in serum up to two hours after dosing.
Their research focusses on the premise that tumourigenic cells are physiologically different to healthy cells, and use modified metabolic signalling pathways to support hyperproliferation and survival. By focussing on molecular systems, Joubert’s group targets the modified metabolic signalling pathways of tumourigenic cells, thereby providing exciting new avenues for the treatment of cancer.
Professor Joubert’s further research, involving both national and international collaborators, focusses on molecular ‘cross-talk mechanisms’ between induced cell destruction and cell death, and the in vivo efficacy of anti-cancer drugs to target cancerous cells at low dosages and at less frequent treatment intervals.
From left: Annie Joubert, Sandra Tatchum and Michelle Visagie. Front: Thandi Mqoco and
Elize Wolmarans.
In high-income countries, common cancers are managed by improved screening, early detection and the transfer of knowledge concerning healthy lifestyles. The fight against cancer is also progressing with the design of drugs that specifically target cancer cells. Conventional chemotherapy and radiation cancer treatments have an impact on both malignant, as well as healthy cells, leading to severe side effects.
Professor Annie Joubert, Head of the Department of Physiology, is taking a different approach in the fight against cancer by investigating novel compounds that prevent cancer cells from multiplying and spreading, while leaving healthy cells unharmed. Currently, Annie Joubert’s
team is focussing on in vitro cellular and molecular studies to assess the potential anti-cancer activity of these agents against cervical and breast cancer cells.
The research team has been working on modifying 2-methoxyestradiol (2ME) to increase oral bioavailability. Increased oral bioavailability limits the rapid hepatic first pass metabolism
of the steroid analogue. Working with Professor Fourie Joubert from the Centre for Bioinformatics and Computational Biology,
Annie Joubert’s laboratory used
in silico modelling to design novel sulphamoylated estrogen analogues (ESE-16, ESE-15-one, ESE-15-ol) which have also been synthesised by a pharmaceutical company. In
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