Chelidonium majus L. alkaloid extract encapsulated in human serum albumin nanoparticles induces mitochondria-mediated apoptosis in HeLa cell line.

Abstract

Interest in herbal medicines as complementary therapies has increased because of concerns regarding the adverse effects of conventional chemotherapeutic agents. Chelidonium majus L. (C. majus) exhibits antiproliferative activity against several cancer cell lines; however, its therapeutic efficacy may be limited by poor bioavailability. This study evaluated the apoptotic activity of C. majus alkaloid extract encapsulated in human serum albumin nanoparticles (C. majus/HSA-NPs) in HeLa cervical cancer cells. Cytotoxicity of C. majus alkaloid extract (C. majus/AE), C. majus/HSA-NPs, and HSA-NPs was determined using the MTT assay in HeLa and human fibroblast cells, apoptosis was quantified by Annexin V/PI flow cytometry, and the mRNA expression of Bax, Bcl-2, caspase-9 and caspase-3 was analyzed by real-time RT-PCR. After 48 h, the IC₅₀ values in HeLa cells were 70.79 μg/mL for C. majus/AE, 52.37 μg/mL for C. majus/HSA-NPs, and >2000 μg/mL for HSA-NPs, whereas fibroblast cells exhibited substantially higher IC₅₀ values (835 μg/mL for C. majus/AE and >1600 μg/mL for both C. majus/HSA-NPs and HSA-NPs), indicating selective cytotoxicity toward cancer cells. C. majus/HSA-NPs induced significantly greater apoptosis than the free alkaloid extract and markedly enhanced the expression of the pro-apoptotic genes Bax, caspase-9, and caspase-3, while suppressing Bcl-2, resulting in a significantly higher Bax/Bcl-2 ratio, consistent with activation of the mitochondrial apoptotic pathway. Overall, nanoencapsulation with human serum albumin enhanced the anticancer efficacy of C. majus alkaloids while maintaining low toxicity toward normal fibroblasts, suggesting that C. majus/HSA-NPs represent a promising candidate for targeted cervical cancer therapy, although further in vivo and mechanistic studies are required to confirm their therapeutic potential.