(171f) Analysis of a Natural Compound Therapeutic on Engineered Ovarian Cancer Spheroids | AIChE

(171f) Analysis of a Natural Compound Therapeutic on Engineered Ovarian Cancer Spheroids


Gunay, G. - Presenter, University of Oklahoma
Ovarian cancer the most lethal gynecological cancer with fatality to higher than 70% of patients in 5 years after diagnosis1. Tumor cells shed from the primary tumor as single or multicellular and form spheroids within the peritoneal cavity2. Spheroid formation within patient ascites increase cancer cell resistance against anoikis3and anti-cancer drugs4,5. The clinical outcome of ovarian cancer has led to the development of three-dimensional (3D) cell culture to study ovarian cancer6–10. Spheroid models of ovarian cancer has been used to evaluate the effectivity of new anticancer agents11–13.

Developing precision drugs targeting the proliferation of cancer cell is essential for cancer treatment. Natural product compound OSW-1 offers a novel targeting mechanism for cancer cell proliferation. It targets oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4)14–18. ORP4 is a known precision target in cancer and essential for cancer cell viability and proliferation18–20, however, OSBP has no such functionality. OSW-1 has been shown to have a potent cytotoxicity against variety if cancer cell lines in vitro, with an average IC50 of 0.78 nM21.

ORP4 is highly expressed in ovarian cancer according to FANTOM database22. Here, we show the cytotoxic activity of ORP-4 targeting OSW-1 in a panel of ovarian cancer cell lines as well as ovarian cancer spheroids. OSW-1 reduced the expression of ORP4 protein both monolayer and spheroids culture and cytotoxic activity of OSW-1 was correlated with ORP4 levels. Removal of lipids in the extracellular environment which is also a feature of limited amounts of exogeneous cholesterol in non-vascularized tumors23,24, increased the activity of OSW-1. Overall, our results show that natural compound OSW-1 induces cytotoxicity in monolayer and spheroid models of ovarian cancer with a significantly increased effectivity compared to Taxol and Cisplatin and offer a novel path for potential treatment of ovarian cancer.


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