efflux of drug or active role of the DNA repair enzymes. To overcome this obstacle, targeted
therapies are being developed.
Poly (ADP-ribose) polymerase (PARP) is a family of proteins implicated in DNA damage
response by activating Base excision repair (BER) pathway. PARP-1 is the most important
member which is involved in DNA repair, genomic stability, inflammation and cell death. It is
a highly conserved zinc binding protein and uses NAD+ as a substrate during DNA repair. The
inhibition of PARP-1 using pharmacological agents can lead to accumulation of single strand
breaks which will progress to double-strand breaks during cellular replication. The cells are
then unable to efficiently repair the DNA, leading to cell death. Therefore, PARP inhibitors
(PARPi) like PJ34 are a promising class of chemotherapeutic agents in cancers associated with
resistance and recurrence, especially in ovarian cancer .
Another targeted molecule to overcome platinum resistance is Glutathione because it is
observed that resistance is essentially linear with cellular levels of GSH . GSH is a tripeptide
which participates in antioxidant defense mechanism. Its major function is detoxification of
xenobiotics, some endogenous compounds and regulating oxidative stress. Proxidant therapies
including chemotherapeutic agents adds oxidative stimulus to constitutive oxidative stress in
tumor cells, causing collapse of antioxidant systems, leading to cell death. But high levels of
GSH- related enzymes, such as ɣ-glutamylcysteine ligase (GCL) and ɣ-glutamyl-
transpeptidase (GGT) makes neoplastic tissues resistant to chemotherapy. Therefore, GSH-
depleting agents like buthionine sulfoximine (BSO) can be used to sensitize cancer cells to
OV-SAHO cell line were used in the study and treated with different concentrations of CDDP
and PJ34. OV-SAHO cells are immortal human ovarian cancer cells derived from a Japanese
women with stage IIIc adenocarcinoma. Cell lines are used to study nature of the disease, the
effect of drugs, developing vaccines etc. The development of cell lines has made a tremendous
impact in the medical and biological research.
The aim of this project is to determine the inhibitory concentration of cytotoxic drugs CDDP
and PJ34 in vitro.
2. Review of literature
2.1. Epidemiology of ovarian cancer
Ovarian carcinomas are heterogenous group of neoplasms responsible for 6% death in women.
According to Globocan, it is the seventh most commonly diagnosed cancer among women in
the world and the fourth most common in India. Although India has a relatively low incidence