Bixin, an apocarotenoid isolated from Bixa orellana L., sensitizes human melanoma cells to dacarbazine-induced apoptosis through ROS-mediated cytotoxicity

Abstract : Cutaneous melanoma has a high capacity to metastasize and significant resistance to conventional therapeutic protocols, which makes its treatment difficult. The combination of conventional drugs with cytostatic molecules of low toxicity has been shown to be an interesting alternative for sensitization of tumor cells to chemotherapy. In this study, we evaluated the effect of bixin, an abundant apocarotenoid present in Bixa orellana, on the sensitization of human melanoma cells (A2058) to dacarbazine treatment, an anticancer agent clinically used for the therapy of metastatic melanoma. UPLC-DAD-MS/MS analyses of bioactive extracts from B. orellana seeds led to the identification of two new apocarotenoids: 6,8′-diapocarotene-6,8′-dioic acid and 6,7′-diapocarotene-6,7′-dioic acid. After being identified as its major compound, bixin (Z-bixin) was evaluated on A2058 cells expressing the oncogenic BRAF VE600 mutation and resistant to dacarbazine treatment. Bixin promoted growth inhibition, reduced cell migration, induced apoptosis and cell cycle arrest in the G2/M phase. When associated with dacarbazine, bixin restored the sensitivity of A2058 cells to chemotherapy, enhancing its antiproliferative, anti-migratory and pro-apoptotic effects. Combined treatment also induced higher ROS (reactive oxygen species) and MDA (malondialdehyde, a lipid peroxidation marker) generation than monotreatment, suggesting that the oxidative stress caused by bixin contributes significantly to its sensitizing effect. Taken together, these data suggest that bixin exerts intrinsic antimelanoma activity by mechanisms complementary to those of dacarbazine, encouraging its use in combined therapy for cutaneous melanoma treatment.
Complete list of metadatas

Cited literature [71 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02074546
Contributor : Laurent Picot <>
Submitted on : Wednesday, March 20, 2019 - 5:01:39 PM
Last modification on : Thursday, April 11, 2019 - 4:02:49 PM
Long-term archiving on: Friday, June 21, 2019 - 10:04:29 PM

Files

Paper for submission FCT (revi...
Files produced by the author(s)

Identifiers

Collections

Citation

Raimundo Gonçalves de Oliveira Júnior, Antoine Bonnet, Estelle Braconnier, Hugo Groult, Grégoire Prunier, et al.. Bixin, an apocarotenoid isolated from Bixa orellana L., sensitizes human melanoma cells to dacarbazine-induced apoptosis through ROS-mediated cytotoxicity. Food and Chemical Toxicology, Elsevier, 2019, 125, pp.549-561. ⟨10.1016/j.fct.2019.02.013⟩. ⟨hal-02074546⟩

Share

Metrics

Record views

93

Files downloads

452