Pharmaceutical composition for preventing and inhibiting liver cancer metastasis containing NSC-38270 as an active ingredient

Olivomycin isomer metastasis inhibitor that prevents liver cancer cell migration and invasion by suppressing Twist1 and inducing E-cadherin

This technology is a pharmaceutical and health food composition for preventing and inhibiting liver cancer metastasis, containing the structural isomer of the Streptomyces-derived antibiotic Olivomycin A, NSC-38270, or its pharmaceutically acceptable salts as an active ingredient. It also includes a screening method that uses this compound as a positive control to identify metastasis-inhibiting candidates based on their ability to reduce Twist1 expression.

Hepatocellular carcinoma is highly aggressive and spreads rapidly to other organs via the portal vein, leading to difficult treatment and poor prognosis; its domestic incidence rate has not improved over the past 20 years. There has been a lack of drugs directly targeting epithelial-mesenchymal transition (EMT), the starting point of metastasis. Furthermore, the Olivomycin A family has limited utility due to high cytotoxicity, and the effects of NSC-38270 on liver cancer metastasis were previously unknown.

This technology leverages the fact that NSC-38270 selectively inhibits liver cancer cell migration and invasion by suppressing the expression of Twist1, a key EMT transcription factor, without affecting Snail1 or Zeb1, while simultaneously upregulating the cell adhesion protein E-cadherin1 (CDH1). It has minimal impact on normal cells and can be formulated as a combination therapy with existing anticancer drugs such as oxaliplatin, cisplatin, and doxorubicin. It can be applied to adjuvant therapy for preventing recurrence and metastasis after liver cancer surgery, combination chemotherapy, and platforms for discovering new metastasis-inhibiting drugs, offering a novel treatment option that blocks the metastatic pathway of hepatocellular carcinoma independently of primary tumor treatment.

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Key Features:

• A pharmaceutical composition for preventing and inhibiting liver cancer cell metastasis comprising the NSC-38270 compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient
• An active ingredient that suppresses the expression of the EMT-TF gene Twist1 and induces the expression of the E-cadherin1 (CDH1) gene
• A pharmaceutical composition further comprising an anticancer agent selected from oxaliplatin, cisplatin, gemcitabine, paclitaxel, and doxorubicin
• A screening step for determining metastasis-inhibiting active substances by comparing Twist1 levels in liver cancer cell lines treated with a positive control compound and candidate substances

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This invention was developed with support from the Ministry of Science and ICT for research on the regulatory mechanisms of transcription factors that control cancer metastasis.

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