Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways

Saudi Pharmaceutical Journal

Lawrence Mabasa¹  Sharon Prince²  Anwar Jardine³  Suparna Chakraborty⁴  K.N. ArulJothi⁴  Luqmaan Mohamed⁴  Leticia V. Costa-Lotufo⁴  Kenza Sayah⁵ 

[1] Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Potheri, Chennai 603203, India;Department of Chemistry, University of Cape Town, Cape Town 7925, South Africa;Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, SP, Brazil;Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa;Medical Research Council, Tygerberg 7505, South Africa;

关键词: Galenia africana (Kraalbos);    Breast cancer;    Cytotoxicity;    Autophagy;    Apoptosis;    Necroptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown