(171f) Analysis of a Natural Compound Therapeutic on Engineered Ovarian Cancer Spheroids
AIChE Annual Meeting
2021
2021 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Poster Session: Pharmaceutical Discovery Development and Manufacturing (PD2M) - Virtual
Tuesday, November 16, 2021 - 10:30am to 12:00pm
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)14â18. ORP4 is a known precision target in cancer and essential for cancer cell viability and proliferation18â20, 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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