Flavokawain A (FKA) represents a novel treatment strategy against synovial sarcoma (SS) by inhibiting the cellular Wnt pathway and changes in apoptosis-related pathways. Aim 1 of the research is to determine whether FKA induces anti-tumor activity in SS by inhibiting Wnt signaling and by modulating apoptosis pathway components. Aim 2 is to assess the efficacy of FKA as a pharmacologic inhibitor in an in vivo model of SS.

• Principal Investigator: Bang H. Hoang, MD
• Organization: Albert Einstein College of Medicine
• Grant Amount: $50,000 – $100,000
• Grant Period: original – 11/1/2016 to 10/31/2017, extended – 11/1/2017 to 4/30/2018

Date of Progress Report: April 30, 2017

Project Description Summary:

Flavokawain A (FKA) represents a novel treatment strategy against synovial sarcoma (SS) by inhibiting the cellular Wnt pathway and changes in apoptosis-related pathways.

Specific Goals and Objectives:

Specific aim 1: To determine whether FKA induces anti-tumor activity in SS by inhibiting Wnt signaling and by modulating apoptosis pathway components. Specific aim 2: To assess the efficacy of FKA as a pharmacologic inhibitor in an in vivo model of SS.

Explanation of Outcomes:

We have been able to treat synovial sarcoma (SS) human cell lines SYO-I and HS-SY-II with increasing doses of FKA and small-molecule Wnt inhibitors LGK974 and C59. After treating with these drugs for 24-72 hours, we performed MTT assays to measure the viability of these cell lines in a time-dependent and dose-dependent manner. We start to examine whether FKA induces apoptosis via the intrinsic or extrinsic pathways. Our preliminary results to date suggest that Bcl-xL is suppressed at a low dose of FKA, suggesting that FKA induces apoptosis at least partially via the intrinsic (mitochondrial) pathway in SS cells.

Greatest Accomplishment:

We have been able to treat synovial sarcoma (SS) human cell lines SYO-I and HS-SY-II with increasing doses of FKA and small-molecule Wnt inhibitors LGK974 and C59. After treating with these drugs for 24-72 hours, we performed MTT assays to measure the viability of these cell lines in a time-dependent and dose-dependent manner.

Greatest Challenge:

The synovial sarcoma cell lines SYO-I and HS-SY-II have been dormant for several years and therefore were difficult to grow in tissue culture at first. However, we persisted and optimized our cell growth conditions several times and now were able to successfully grow these cell lines consistently.

Lessons Learned:

We have learned that working with frozen stocks of synovial sarcoma cell lines SYO-I and HS-SY-II, which have been dormant for several years, would require manipulations of the growing conditions such as frequent feeding and passaging of the cells to optimize growing conditions in order to obtain consistent supplies of cell lines to perform our experiments.

Partnerships and Collaborations:

We are partnering with the University of Utah to conduct experiments to test the in vivo efficacy of FKA compound in a mouse model of synovial sarcoma.

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