Eggplant-derived Solamargin-Propolis nanoformulation as an efficacious chemotherapeutic agent for lung carcinoma A549 through mitochondrial dynamics dysregulation

Abstract

Solamargine, derived from eggplant, has shown significant antitumor effects in preclinical studies, demonstrating its potential for cancer therapy. Its ability to modulate mitochondrial dynamics, induce apoptosis, and inhibit metastasis underscores its potential as an anticancer agent. The present study investigated the effectiveness of solamargine (Sm) extracted from eggplant and self-assembled with propolis nanoparticles (PNP) through an acid-base neutralization reaction to fabricate encapsulated Sm (Sm-PNP) for fighting lung cancer by disrupting mitochondrial fission/fusion dynamics. Spectral and microscopic analyses confirmed the formation of Sm-PNPs, wherein solamargine (Sm) was encapsulated within propolis nanoparticles (PNP). Solanine (SA) (31.5 ± 3.5), Sm (17.77 ± 2.3), and Sm-PNP (17.325 ± 3.62) showed significantly lower cytotoxic IC₅₀ concentrations against A549 lung carcinoma cells than PNP (99.825 ± 17.5) (P < 0.0001). In contrast, these substances showed higher IC50 values in HeLa cells, without statistically significant differences, suggesting a preferential effect on cancer cells. Sm-PNP treatment progressively upregulated Drp1 and Fis1 (P < 0.001) in A549 cells, whereas Mfn1 and 2 showed significant differences in inhibition across groups (P < 0.01). This suggests the potential of encapsulated solamargine as an effective cancer therapy, providing insights into MFN1 and 2's roles and alternative treatments. Compared to untreated A549 cells and cisplatin (reference drug), Cyto C, Bax (P < 0.01), and caspase 8 (P < 0.001) gene expression was significantly upregulated, with varying values. Sm-PNP significantly inhibited the inflammatory cytokines TNFα (P < 0.01) and IL10 (P < 0.05) and enhanced apoptotic activity by upregulating P53 expression (P < 0.0001) and inhibiting ATPase inhibitory factor 1 (P < 0.001). Consequently, the encapsulated form of solamargine increased its bioavailability and could therefore serve as a promising approach for enhancing apoptosis in lung cancer by disrupting the balance of mitochondrial dynamics.