Artepillin C is the main compound present in propolis from Baccharis dracunculifolia, whose antitumor activity has been the focus of many studies. Herein, we shall investigate the Artepillin C mechanisms of action against cells derived from the oropharyngeal carcinoma (HEp-2). Cytotoxicity tests revealed that the concentrations of Artepillin C required to reduce cell viability by 50% (CC₅₀) are dependent on the incubation time, decreasing from 40.7 × 10⁻⁵ mol/L to 15.7 × 10⁻⁵ mol/L and 9.05 × 10⁻⁵ mol/L considering 12, 24 and 48 h, respectively. Hydrophobic interactions on neutral species of Artepillin C induce aggregation over the HEp-2 plasma membrane, given the acid conditions of the cellular culture. Indeed, Langmuir monolayers mimicking cellular membranes of tumor cells revealed Artepillin C affinity to interact with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) containing 20 mol% of 1,2-dipalmitoyl-sn-glychero-3-phosphoserine (DPPS), leading aggregation on giant unilamellar vesicles (GUVs) at pH 3.2. Moreover, leakage experiments on GUVs have shown that the presence of DPPS enhances the efflux of the fluorescent probe signaling the membrane permeabilization, which is the origin of the necrotic pathway triggered in HEp-2 cells, as observed by flow cytometry assays.

青霉素C是来自德氏杆菌的蜂胶中存在的主要化合物，其抗肿瘤活性已成为许多研究的重点。在本文中，我们将研究Artepillin C对口咽癌（HEp-2）细胞的作用机制。细胞毒性测试表明，使细胞活力降低50％（CC ₅₀）所需的Artepillin C浓度取决于孵育时间，从40.7×10 ^-5  mol / L降至15.7×10 ^-5  mol / L和9.05× 10 ^-5 mol / L，分别考虑12、24和48小时。考虑到细胞培养的酸性条件，在中性青蒿素C上的疏水相互作用诱导了HEp-2质膜上的聚集。确实，模仿肿瘤细胞细胞膜的Langmuir单层膜显示青霉素C亲和力与含有20 mol％1,2-二棕榈酰-sn-glychero-3-的1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）相互作用。磷酸丝氨酸（DPPS），导致聚集在pH 3.2的巨型单层囊泡（GUV）上。此外，在GUV上的泄漏实验表明，DPPS的存在增强了荧光探针的信号通透性，表明膜通透性，这是流式细胞术检测到的HEp-2细胞中触发的坏死途径的起源。