Jamshed Iqbal1, Syeda Abida Ejaz2, Imtiaz Khan3, Elina Ausekle4, Mariia Miliutina4, Peter Langer4,4. 1. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan. drjamshed@ciit.net.pk. 2. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan. 3. Department of Chemistry, Quaid-i-Azam University, -45320, Islamabad, Pakistan. 4. Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059, Rostock, Germany.
Abstract
BACKGROUND: Among the different types of cancers, breast cancer, bone cancer and cervical cancer are the most common gender specific cancer types that are affecting the women worldwide. Currently, many enzymatic and cellular pathways are known as drug targets for the treatment of cancer. Even though many improvements have been made in the therapy of various types of cancer, but the major disadvantage of available anti-cancer drugs is their non-selective behavior towards cancer cells as well as normal cells. OBJECTIVES: In the light of this fact, the searching of new compounds with selective behavior only towards cancer cells is critically important. Previously, we have identified several series of compounds as the potential inhibitors of these families. METHODS: Herein, we investigate quinolones and quinolines for their anti-cancer activity against breast cancer cells (MCF-7), bone marrow cancer cells (K-562) and cervical cancer cells (HeLa) by MTT assay. The most effective derivatives were further subjected to flow cytometry analysis followed by fluorescence microscopic analysis by using 4´,6-diamidine-2´-phenylindole (DAPI) and propidium staining (PI) staining. RESULTS: All the tested compounds were found selective only towards cancer cells. The identified compounds also induced either G2 or S-phase cell cycle arrest within the respective cancer cell line, chromatin condensation and the nuclear fragmentation, as well as maximum interaction with DNA. CONCLUSIONS: These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs. Graphical abstract Flow cytometric analysis of cell cycle using propidium iodide staining. Cell apoptosis observed under fluorescence microscope using DAPI and PI staining.
BACKGROUND: Among the different types of cancers, breast cancer, bone cancer and cervical cancer are the most common gender specific cancer types that are affecting the women worldwide. Currently, many enzymatic and cellular pathways are known as drug targets for the treatment of cancer. Even though many improvements have been made in the therapy of various types of cancer, but the major disadvantage of available anti-cancer drugs is their non-selective behavior towards cancer cells as well as normal cells. OBJECTIVES: In the light of this fact, the searching of new compounds with selective behavior only towards cancer cells is critically important. Previously, we have identified several series of compounds as the potential inhibitors of these families. METHODS: Herein, we investigate quinolones and quinolines for their anti-cancer activity against breast cancer cells (MCF-7), bone marrow cancer cells (K-562) and cervical cancer cells (HeLa) by MTT assay. The most effective derivatives were further subjected to flow cytometry analysis followed by fluorescence microscopic analysis by using 4´,6-diamidine-2´-phenylindole (DAPI) and propidium staining (PI) staining. RESULTS: All the tested compounds were found selective only towards cancer cells. The identified compounds also induced either G2 or S-phase cell cycle arrest within the respective cancer cell line, chromatin condensation and the nuclear fragmentation, as well as maximum interaction with DNA. CONCLUSIONS: These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs. Graphical abstract Flow cytometric analysis of cell cycle using propidium iodide staining. Cell apoptosis observed under fluorescence microscope using DAPI and PI staining.
Entities:
Keywords:
Bone marrow cells (K–562); Breast cancer cells (MCF–7); Cell-cycle; Cervical cancer cells (HeLa); Quinolines; Quinolones
Authors: Goodarz Danaei; Stephen Vander Hoorn; Alan D Lopez; Christopher J L Murray; Majid Ezzati Journal: Lancet Date: 2005-11-19 Impact factor: 79.321