Tualang Honey Promotes Apoptosis of the A549 Lung Adenocarcinoma Cell Line via Modulation of PI3K/AKT Signaling Pathway-Related Proteins

The phosphatidylinositol 3-kinases (PI3Ks)/protein kinase B (AKT) signaling pathway is frequently overexpressed in lung adenocarcinoma and associated with carcinogenesis through cell proliferation, and apoptosis deactivation; and it also enhances chemotherapeutic drugs resistance. Tualang honey (TH) has proven anticancer property on lung adenocarcinoma. However, the underlying mechanisms remain unreported. Hence, this study investigates the apoptosis-inducing effect of TH on A549 lung adenocarcinoma cell line using RayBio (R) Human Apoptosis Array and label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to elucidate the modulation of upstream and downstream proteins of PI3K/AKT signaling pathway. The apoptosis-promoting effects of TH were associated with (i) the upregulation of pro-apoptotic proteins (i.e. cytochrome c, histone H1.2, and histone H1.4) and tumor suppressor proteins (i.e. IGFBP-3 and IGFBP-5), and (ii) downregulation of XIAP, insulin-growth factor (IGF) system (i.e. IGF-1, IGF1R, IGFBP-1, IGFBP-2, and IGFBP-4), HSP90AB1, YWHAQ, endoplasmin, and ITGB1. The effects were also linked with the suppression of receptor tyrosine kinase, integrins, G proteins, CHUK, RAC1, and JAK. Thus, TH may promote apoptosis of A549 lung adenocarcinoma cell line through alteration of the PI3K/AKT signaling pathway-related proteins. However, further studies involving animal models to provide a better model of understanding would prove necessary.