INTRINSIC MITOCHONDRIAL APOPTOTIC PATHWAYS; AN IMPERATIVE FEATURE OF CISPLATIN CYTOTOXICTY
AbstractUp till now, the most thriving and extensively used antineoplastic agent with well-established effectiveness is cisplatin. Being a non-specific drug, it reacts not only with genomic DNA but also binds and damages the plasma protein and cytoplasmic protein that confers to cisplatin resistance and severs side effects. DNA damage prompted by cisplatin leads to the activation of many signaling cascades that clue to cell death. This review work comprises interactive pathways of cisplatin with mitochondrial proteins such as p53, p38, p73 and c-Abl which contribute their role in cell death. In addition, disturbance in drug efflux and influx and competent role of repair protein also share in cisplatin resistance. Inhibition of Akt, MKPI, cabl stimulation, amplified activity of p53, p73, and MAPK, increased expression of pro apoptotics (Bax, Bck, Bcd) and decreased expression of anti apoptotic pointers to cisplatin sensitivity. Innovative creation or amendment in a platinum based drug which can magnify the numerous advantageous pathways and precisely constrains the various undesired pathways would greatly contribute to conquest against cancer fight.
Article Information
3
31-41
759KB
1152
English
IJPSR
Maria Fareed Siddiqui*, Esha Sadiq and M.H. Qazi
Centre for Research in Molecular Medicine (CRiMM), University of Lahore, 1 km Defense Road Lahore, Pakistan.
maria.pharmacist@gmail.com
11 May, 2014
09 August, 2014
29 August, 2014
http://dx.doi.org/10.13040/IJPSR.0975-8232.6(1).31-41
01 January, 2015
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