Discovery of anti-cancer drug in yeast focuses on screening and identifying compounds that can target ‘cancer-specific’ biological processes while causing less toxicity to non-cancerous cells.
By Zainab Javed and Ayesha Yasin
Discovery of anti-cancer drug in yeast focuses on screening and identifying compounds that can target ‘cancer-specific’ biological processes while causing less toxicity to non-cancerous cells. Nature is so complex that natural molecules used for treating various diseases i.e. cancer, viral infection still can’t be produced chemically. Today, major chemical and pharmaceutical companies harvest yeast (Saccharomyces cerevisiae) in order to extract valuable substances like anti-cancer drug.
Figure 1: Yeast as a model system for anticancer drug discovery
Cancer is the uncontrolled abnormal cells growth in any part of body. These abnormal cells are termed as cancer cells, malignant cells, or tumor cells. A lot of people died all over the world due to cancer. About 8.2 million deaths is due to cancer.
Yeast have highly conserved cancer-related cellular processes relative to human cells and thus offer new opportunities for anticancer drug discovery when combined with chemical screening. With the identification of DNA topoisomerases as the targets of a variety of therapeutics including anticancer drugs, structural and mechanistic studies of these enzymes, especially human DNA topo isomerases, have assumed added significance. Presently, three human DNA topoisomerases are known. Human DNA topo isomerase I, the target of an antitumor, characterized by its transient breakage of DNA strands one at a time. Human DNA topoisomerases II alpha and II beta are two closely related members of the type II DNA topoisomerase family. Many studies with mammalian cell lines and purified enzymes indicated that a large number of anticancer drugs, including mAMSA, VM-26, VP-16, merbarone, and bis(2,6-dioxopiperazine) derivatives, act on one or both of the alpha and beta variants of human DNA topoisomerase II.
Figure 2: anti-cancer drug discovery using yeast
The genes TOPI, TOP2 alpha, and TOP2 beta encoding the human DNA topoisomerases have been cloned and mapped to chromosomal locations 20ql2, l7q2l-22, and 3p24 respectively. Functional human DNA topoisomerase 1 can be expressed in yeast from cloned human TOPI CDNA, and appropriate yeast strains expressing human instead of yeast DNA topoisomerase I have also been constructed to provide a convenient system for mutational studies, drug screening, and analysis of the mechanisms of cell killing by drugs acting on the human enzyme. Overexpression of human DNA topoisomerase II alpha in yeast and purification of the enzyme to near homogeneity have also been achieved. Yeast is valuable complementary alternatives to cellular and in vitro screening systems. Their genetic amenability, low price, and culture conditions and circumstances are compatible with large-scale screening make it useful models for drug discovery
Figure 3: anti-cancer drug production using yeast
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Authors: Zainab Javed and Ayesha Yasin, Biotechnology Department, Kinnaird College for Women University, Lahore.