Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma
Mathieu Boulin1, Séverine Guiu, Bruno Chauffert
1Department of Pharmacy, CHU (University Hospital), Dijon, France. mathieu.boulin@chu-dijon.fr
Abstract:
The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.
Insights
Idarubicin demonstrated superior in-vitro cytotoxicity against hepatocellular carcinoma (HCC) cell lines compared to 10 other anticancer drugs. This study identifies idarubicin as a promising candidate for transarterial chemoembolization in HCC treatment.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide.
- Transarterial chemoembolization (TACE) is a common locoregional therapy for unresectable HCC.
- Optimizing drug selection for TACE is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the in-vitro cytotoxic activity of 11 anticancer drugs on three human HCC cell lines.
- To identify the most effective drug candidate for transarterial chemoembolization in HCC.
- To compare the efficacy of idarubicin against other chemotherapeutic agents.
Main Methods:
- In-vitro cytotoxic evaluations were performed on SNU-398, HepG2, and SNU-449 human HCC cell lines.
- Eleven anticancer drugs were tested at various concentrations using a quantitative colorimetric assay.
- The drug concentration causing 90% cell death (IC90) and cytotoxic index (CyI) were calculated and analyzed using nonlinear regression models.
Main Results:
- Idarubicin exhibited the highest cytotoxic activity across all three tested HCC cell lines.
- Idarubicin's cytotoxic index (CyI) was significantly higher than other agents, including doxorubicin, epirubicin, and gemcitabine.
- Idarubicin demonstrated effectiveness even on the resistant SNU-449 cell line, outperforming paclitaxel and gemcitabine.
Conclusions:
- Idarubicin is the most potent chemotherapeutic agent among the 11 tested for hepatocellular carcinoma cell lines in-vitro.
- Idarubicin shows significant promise as a candidate drug for transarterial chemoembolization in HCC.
- Further clinical studies are warranted to confirm the safety and efficacy of idarubicin in TACE for HCC patients.
