Although most ovarian cancer patients initially respond to cytoreductive surgery and adjuvant paclitaxel and platinum based chemotherapy, the major ity will experience disease recurrence. The response rate to current second line or third line chemotherapy is less than 33% due to the rise of resistance to these drugs. Hence www.selleckchem.com/products/Axitinib.html there is a need for more effective therapies and or treat ment approaches to overcome drug resistance. New drug discovery demands enormous cost and time. An alternative approach is Drug Repurposing wherein clinically approved drugs for one indication are re explored for new applications. It is well known that many drugs ex hibit polypharmacological properties, and hence can be ex plored for their ability to modulate new alternate targets.

Drug repurposing is a cost effective alternative to new drug discovery as ADME and basic toxicity are already well established and can be immediately taken Inhibitors,Modulators,Libraries to Phase II III clinical trials. However, Inhibitors,Modulators,Libraries in order to repurpose these drugs for novel targets diseases, it is essential to first understand the basic biological action and mechanism of action in preclinical and animal models. In our present study, we focused on Bithionol, a clinically approved anti parasitic drug as an anti ovarian cancer drug. Bithio nol has received Food and Drug Administration Inhibitors,Modulators,Libraries ap proval as a second line orally administered medication for the treatment of helminthic infection and has been safely dosed in humans. All the details of toxicology and pharmacokinetic properties for BT are available.

BT was shown to be an effective anti cancer agent in preclinical models and is safe in non cancer patients. BT was shown to decrease tumor weight in a breast cancer model and reduced metastases of tumors initiated with A2058 melanoma cells. BT was re ported to reduce melanoma cell migration in a dose dependent Inhibitors,Modulators,Libraries fashion when assayed using in vitro cell migration and invasion systems. Similar observa tions were reported in the case of breast and ovarian cancer cell lines. BT was also reported to show an inhibitory effect on cervical cancer cell growth during in vitro screening. Inhibitors,Modulators,Libraries These previous studies have pro posed possible mechanisms of action of BT against can cer cells. Autotaxin inhibition was proposed as a mechanism of action to decrease tumor in a pre clinical melanoma model.

An additional mechanism was inhibition of NF kB selleck bio signalling via inhibition of IB phosphorylation and caspase 3 7 induction. Based on these significant observations, we seek a better un derstanding of the effect BT on ovarian cancer cell lines, and specifically on cisplatin resistant cell lines. The objective of the present study was to explore the cytotoxic effects of BT against ovarian cancer cell lines and to further delineate the cellular mechanism of cytotoxicity. First, we studied the cytotoxic effect against a panel of ovarian cancer cell lines exhibiting varying sensitivities to cisplatin.