Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Abstract

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC 50 of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC 50 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells

“…Accordingly, emulsomes were chosen for investigation in this work. In addition, apamin was used for surface-functionalization of the optimized mulsomal formulation to provide additional advantage of enhancing uptake of EGA by cancerous cells [ 35 ]. It is worth noting that the reported cytotoxic activity of bee venom components including apamin could also augment the cytotoxicity of EGA [ 31 ].…”

2‐Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway

“…12 In the past decades, 2ME2 has been considered to be a potential cancer chemotherapeutic agent that is capable of inhibiting cell growth and inducing cell death in malignant cell lines such as colon carcinomas, melanoma, and the lungs. [13][14][15] In recent studies, researchers have found other antitumor mechanisms of 2ME2. Lu's study demonstrated that 2ME2 could inhibit the expression of HIF-1α and confer radiosensitivity in ECA-109 cells.…”

“…This is then followed by a conjugation reaction of the enzyme catechol‐O‐methyltransferase generating 2ME2 from 2‐hydroxyestradiol 12 . In the past decades, 2ME2 has been considered to be a potential cancer chemotherapeutic agent that is capable of inhibiting cell growth and inducing cell death in malignant cell lines such as colon carcinomas, melanoma, and the lungs 13–15 . In recent studies, researchers have found other antitumor mechanisms of 2ME2.…”

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-β1 and p-ERK1/2 Axis

“…However, the therapeutic applications of 2ME are constrained due to its poor solubility which negatively affects its bioavailability and tissue distribution [ 58 , 59 ]. In this regard, loading of 2ME in nanoparticles has been shown to improve its pharmacokinetic and pharmacodynamics characteristics [ 60 , 61 , 62 ]. Thus, this study aimed at evaluating the potential of 2ME loaded TPGS micelles to prevent CSA-induced nephrotoxicity in rats.…”