Planta Med 2021; 87(15): 1305
DOI: 10.1055/s-0041-1736958
Abstracts
8. Poster Contributions
8.9 Recent Advances in Medicinal Plant and Natural Product Research

Chemosensitizing properties of ß-caryophyllene oxide in hepatocellular carcinoma

S Di Giacomo
1   Dept. Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
,
O Briz
2   Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
,
M J Monte
2   Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
,
L Sanchez-Vicente
2   Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
,
M Eufemi
3   Dept. Biochemical Science "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
,
E Lozano
2   Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
,
A Di Sotto
1   Dept. Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
,
Marin JJG
2   Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
› Author Affiliations
› Further Information
 

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor, often associated with multidrug resistance, which limits the efficacy of conventional anticancer drugs [1]. In the last years, the possibility to affect tumour growth with multi-target therapies acting in synergy or on different targets has been highlighted. This approach enables to increase low-dose anticancer drug efficacy and limit systemic toxicity. In present study, the ability of the natural sesquiterpene ß-caryophyllene oxide (CRYO) to enhance the response of HCC to the first-line drug sorafenib (SOR) has been investigated.

The cytotoxicity of CRYO alone or in combination with SOR was evaluated by MTT assay in different HCC cells [2] [3]. Moreover, its ability to modulate both activity and expression of Pgp, MRP1/2 and STAT3 was measured[2] [3]. At last, the sorafenib chemosensitization by the natural sesquiterpene was assessed in a liver xenograft model [2]. Despite a low cytotoxicity in our cellular models, CRYO was able to synergistically increase HCC cell sensitivity to SOR. CRYO also inhibited Pgp and MRP1/2 activity and reduced the SOR-induced expression of Pgp, MRP1/2 and STAT3 (Ser 727). In vivo experiments highlighted the combination of CRYO and SOR was able to inhibit the tumor growth of about 58%, despite a null effect of the anticancer drug alone.

In conclusion, our results highlight the possible role of CRYO as a chemosensitizing agent in combination with SOR and support its potential usefulness to reverse the sorafenib-induced multidrug resistance by targeting Pgp and MRP1/2 transporters, and/or the STAT3 pathway.



Publication History

Article published online:
13 December 2021

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