Globally, breast cancer is the most common malignancy in women and the second most common cause of cancer-related death among women. There is therefore a need to identify more efficacious therapies for this neoplasm. Galenia africana (Kraalbos) is a perennial shrub found in Southern Africa and is used by the indigenous people to treat various ailments. There has therefore been much interest to establish the scientific basis for the medicinal properties of Kraalbos. This study aimed to investigate and characterise the anti-cancer activity of an ethanolic extract of Kraalbos leaves, KB2, against oestrogen receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. LC-MS/MS analyses identified the phytochemicals 7′-hydroxyflavanone, 5′,7'-dihydroxyflavanone, 2′,4′-dihydroxydihydrochalcone and 2′,4′-dihydroxychalcone in KB2. KB2 exhibited an IC₅₀ of 114 µg/ml and 130.5 µg/ml in MCF-7 and MDA-MB-231 cells respectively, selectively inhibited their long-term survival and reduced their migration which correlated with a decrease in EMT markers. It induced oxidative stress (ROS), DNA damage (increased levels of γ-H2AX), and triggered cell cycle arrests in MCF-7 and MDA-MB-231 cells. Importantly, KB2 activated intrinsic (cleaved caspase 9) and extrinsic (cleaved caspase 8) apoptosis, necroptosis (p-RIP3 and the downstream target of the necrosome, pMLKL) and autophagy (LC3II). Co-treatment of the breast cancer cells with KB2 and the autophagy inhibitor bafilomycin A1 resulted in a significant increase in cell viability which suggests that KB2 induced autophagy is a cell death mechanism.

在全球范围内，乳腺癌是女性最常见的恶性肿瘤，也是女性癌症相关死亡的第二大最常见原因。因此，需要针对该肿瘤鉴定更有效的疗法。非洲（Kraalbos）是在南部非洲发现的多年生灌木，被土著人民用来治疗各种疾病。因此，人们非常有兴趣为Kraalbos的药用特性建立科学依据。这项研究旨在调查和表征Kraalbos叶子KB2的乙醇提取物对雌激素受体阳性（MCF-7）和三阴性（MDA-MB-231）乳腺癌细胞的抗癌活性。LC-MS / MS分析鉴定了KB2中的植物化学物质7'-羟基黄酮，5'，7'-二羟基黄酮，2'，4'-二羟基二氢查耳酮和2'，4'-二羟基查耳酮。KB2展示了IC ₅₀分别在MCF-7和MDA-MB-231细胞中分别检测到114 µg / ml和130.5 µg / ml可以选择性抑制其长期存活并减少其迁移，这与EMT标记物的减少有关。它诱导了氧化应激（ROS），DNA损伤（γ-H2AX水平升高），并触发了MCF-7和MDA-MB-231细胞的细胞周期停滞。重要的是，KB2激活内在的（裂解的caspase 9）和外在的（裂解的caspase 8）凋亡，坏死性坏死（p-RIP3和坏死体的下游靶标pMLKL）和自噬（LC3II）。与KB2和自噬抑制剂bafilomycin A1共同治疗乳腺癌细胞会导致细胞活力显着增加，这表明KB2诱导的自噬是细胞死亡的机制。