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BackgroundEpithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer.Methods/Principal FindingsUsing patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics.ConclusionThe present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

Nanotechnology is an evolving field with enormous potential for biomedical applications. The growing interest to use inorganic nanoparticles in medicine is due to the unique size and shapedependent optoelectronic properties. Herein, we will focus on gold, silver and platinum nanoparticles, discussing recent developments for therapeutic applications with regard to cancer in terms of nanoparticles being used as a delivery vehicle as well as therapeutic agents. We will also discuss some of the key challenges to be addressed in future studies. IntroductionNanotechnology is a flourishing area with several interdisciplinary fields, such as medicine, electronics, and biomaterials (1). The long-term goal of nanomedicine is to revolutionize the health care system by fighting deadly diseases in more efficient ways (1). Gold nanoparticles are being investigated for biological applications due to their biocompatibility (1,2). In this review, we will focus on gold and a few other inorganic nanoparticles and discuss their potential applications in therapy and imaging. Gold nanoparticles have been used mostly as a probe for electron microscopy and as a delivery vehicle for biomolecules. However, the use of nanoparticles as a therapeutic agent is relatively new. Among all the nanomaterials, gold has attracted wide attention due to its relative non-toxic nature (2-5). Gold has been shown to have strong affinity to thiol and amine functionalities (2). Such affinity enables surface modifications to gold nanoparticles relatively easily through Au-S and Au-N bonding with targeting agents and/or chemotherapeutics that possess these functionalities (2). Thus, through intelligent design it is possible to develop multifunctional nanoparticles that could potentially increase the efficiency of detection, diagnosis and therapy (2,3). Application of Gold in Ancient MedicineGold compounds were used by Chinese and Indian cultures as early as 2500-2600 BC in the form of "Swarna Bhasma," a gold based medicine, for various purposes such as increasing vital power and curing male impotence (4-6). In the early 19 th and 20 th centuries gold compounds were utilized for the treatment of epilepsy, syphilis, rheumatic diseases, * Corresponding Author: Priyabrata Mukherjee, Ph.D, Department of Biochemistry and Molecular Biology, Department of Biomedical Engineering, Cancer Center, Mayo Clinic, Rochester, MN-55905, mukherjee.priyabrata@mayo.edu, Phone: 507-284-8563, Fax: 507-293-1058. NIH Public Access Synthesis of NanoparticlesPreparation of gold nanoparticles (AuNP) of different sizes and shapes are well documented (2,5,15,16 Physio-Chemical Properties of Metal NanoparticlesThe tunablility of optoelectronic properties through shape and size-dependent properties make inorganic nanomaterials unique for various biomedical applications (33)(34)(35)(36). Inorganic nanoparticles such as gold, silver and copper possess brilliant colors due to the presence of [39][40][41][42][43]. AuNPs show a strong SPR band that is dependent on particle size (...

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