Şumnulu, Deniz

DOI: PMID:

Abstract

Background: The study demonstrated that 89.72 µg/mL Theranekron D6 (TD6), 62.46 µM Tanshinone IIA (Tansh), and both Tansh-TD6 (Mix) exhibited selective apoptotic mechanisms on HEL299, A549, and Hep3B cells. Materials and methods: Application doses were determined by MTT assays. Apoptotic and ROS-affected cells were assessed via flow cytometry, gene expression changes by qRT-PCR, and mitochondrial membrane potential alterations through fluorescence microscopy. Results: Tansh reduced cell viability in all three cell lines, whereas the application of Mix increased cell viability in HEL299 cells, had no effect on A549 cells, and significantly decreased viability in Hep3B cells. This situation has also shown similarities in studies on ROS, mitochondrial membrane potential, and apoptosis. qRT-PCR analysis showed that in HEL299, Tansh, TD6, and Mix upregulated XIAP (2.42-fold, 1.4-fold, and 1.72-fold) and c-IAP1(2.97-fold, 1.44-fold, and 1.67-fold), whereas SMAC induction by Tansh was attenuated in the Mix (2.49-fold to 1.45-fold). In A549, Tansh strongly upregulated XIAP (3.86-fold), c-IAP1 (5.14-fold), and SMAC (5.02-fold), while TD6 downregulated them (0.4-fold, 0.68-fold, and 0.58-fold). In Hep3B, XIAP (0.63-fold, 0.61-fold, and 0.29-fold) and c-IAP1 (0.3-fold, 0.36-fold, and 0.08-fold) were consistently downregulated with all appplication, while SMAC expression was markedly elevated with Tansh (5.23-fold), TD6 (3.46-fold), and Mix (8.59-fold) applications. Apoptosis increased in HEL299 with Tansh (59.62%) but decreased with Mix (17.56%), whereas in Hep3B it rose with Mix (50.76% to 59.75%). Conclusion: TD6 enhances or sustains anticancer activity in malignant cells, suggesting therapeutic potential in combination strategies for many types of cancers.

Keywords

ROS ; SMAC ; Tanshinone IIA ; Theranekron D6

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