Tomentosin Potentiates Cisplatin-Induced Apoptosis and Modulates Proteostasis-Related Proteins in A549 Lung Cancer Cells

Abstract

Lung cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for improved therapeutic strategies and adjunct treatment approaches. In this study, we investigated the anticancer effects of tomentosin in A549 cells and evaluated the cellular response to its combined exposure with cisplatin. Cell viability was assessed using the WST-1 assay in A549 and BEAS-2B cells. Apoptosis was evaluated by Annexin V-FITC/PI staining, cell-cycle distribution by flow cytometry, and caspase-3/7 activity by a flow cytometric assay. In addition, intracellular levels of the proteostasis-related proteins p97/VCP, SVIP, and p62/SQSTM1 were quantified by flow cytometry. Tomentosin reduced A549 cell viability in a dose- and time-dependent manner, with a 24 h IC50 value of 24.46 ± 1.61 µM, while producing a comparatively lower cytotoxic response in BEAS-2B cells. Tomentosin increased apoptotic cell populations and altered cell-cycle distribution. Combined exposure to tomentosin and cisplatin resulted in an early apoptotic population of 72.58 ± 0.47%, compared with 2.06 ± 0.11% in control cells, and was associated with greater caspase-3/7 activity than either treatment alone. Tomentosin and/or cisplatin also produced significant alterations in p97/VCP, SVIP, and p62 levels. These findings indicate that tomentosin exerts antiproliferative and pro-apoptotic effects in A549 cells and that combined exposure with cisplatin is associated with a greater biological response under the investigated in vitro conditions. The accompanying changes in p97/VCP, SVIP, and p62 suggest modulation of proteostasis-associated cellular responses; however, their functional contribution to the treatment response remains to be established.