Abstract
Anthracyclines are frequently used to treat many cancers including triple negative breast cancer, which is commonly observed in African-American women (AA), and tend to be more aggressive, carry worse prognoses, and are harder to manage because they lack molecular targets. Although effective, anthracyclines use can be limited by serious side effects and eventually the development of drug resistance. In S. cerevisiae, mutants of HOM6 display hypersensitivity to doxorubicin. HOM6 is required for synthesis of threonine and interruption of the pathway leads to accumulation of the threonine intermediate L-aspartate-semialdehyde. This intermediate may synergize with doxorubicin to kill the cell. In fact, deleting HOM3 in the first step, preventing the pathway to reach the HOM6 step, rescues the sensitivity of the hom6 strain to doxorubicin. Using several S. cerevisiae strains (wild type, hom6, hom3, hom3hom6, ydj1, siz1, and msh2), we determined their sensitivity to aldehydes and to their combination with doxorubicin, cisplatin, and etoposide. Combination of formaldehyde and doxorubicin was most effective at reducing cell survival by 31-fold-39-fold (in wild type cells) relative to doxorubicin and formaldehyde alone. This effect was ...Continue Reading
References
Mar 1, 1985·Biochemical Pharmacology·J M SiegfriedT R Tritton
Dec 1, 1994·Current Opinion in Biotechnology·R D Kolodner, E Alani
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Dec 1, 1995·British Journal of Clinical Pharmacology·K T KivistöM Eichelbaum
Mar 1, 1996·General Pharmacology·D NielsenT Skovsgaard
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·D X TishkoffR D Kolodner
Nov 21, 1998·Leukemia·M L Den BoerA J Veerman
Sep 25, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·R CaricchioP L Cohen
Feb 15, 2001·Current Medicinal Chemistry·D J Taatjes, T H Koch
Jul 27, 2001·Analytical Chemistry·S KatoV M Bierbaum
Dec 1, 2001·Clinical Immunology : the Official Journal of the Clinical Immunology Society·I Laux, A Nel
Jun 1, 2004·Pharmacological Reviews·Giorgio MinottiLuca Gianni
Sep 24, 2005·Current Medicinal Chemistry. Anti-cancer Agents·S M CuttsD R Phillips
Apr 14, 2007·Molecular Cancer Therapeutics·Suzanne M CuttsDon R Phillips
Dec 7, 2007·Cancer Research·Ling XiaHernan Flores-Rozas
Sep 10, 2009·Biochemical Pharmacology·Michal UgarenkoSuzanne M Cutts
Jan 26, 2010·Critical Reviews in Oncology/hematology·Claudia AndreettaFabio Puglisi
May 17, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Beshay N M ZordokyAyman O S El-Kadi
Aug 8, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Abdulaziz M S AlsaadAyman O S El-Kadi
Nov 21, 2012·Pediatrics·Steven E LipshultzUNKNOWN Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium
Nov 18, 2014·Frontiers in Oncology·David A AlagpulinsaRobert Joseph Shmookler Reis
Jul 8, 2015·The Lancet Oncology·Natalie TurnerAngelo Di Leo
Jan 31, 2016·Molecular Cancer Therapeutics·Natalie A Jabbour-LeungKhandan Keyomarsi
Oct 9, 2016·Biopolymers·E F SilvaM S Rocha
Feb 12, 2017·Cardiovascular Drugs and Therapy·John V McGowanDerek M Yellon
May 31, 2017·BioMed Research International·Min XuCheng Lv
Sep 22, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ayman ShafeiMahmoud Ellithy
Sep 30, 2017·Drug Delivery·Yinan ZhongZhiyuan Zhong
Jan 9, 2018·Gene·Hong-Rong FeiFeng-Ze Wang
Feb 10, 2018·Biochimica Et Biophysica Acta. General Subjects·Kyung-Hwa JeonYoungjoo Kwon
Feb 24, 2018·Oncogenesis·Marta Di MartileDonatella Del Bufalo
Feb 24, 2018·Biochemical Pharmacology·Jun GuChang-Qian Wang
Feb 24, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shizheng LiKun Li
Mar 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Subhadip HajraSudin Bhattacharya