| 摘要: | Lung cancer, accounting for an estimated 2 million diagnoses and 1.8 million deaths of all global cancer incidences, presents a pressing health challenge with its increasing annual prevalence. The advent of drug resistance underscores the necessity to explore safer, more effective antiproliferative agents. Although primary health care provision in many developing countries is becoming more Westernized in some aspects, traditional medicines (TMs) still have significant backing, especially in rural or isolated areas. Annona muricata (AM) leaves have demonstrated potential anticancer and anti-inflammatory properties against several cancer cell lines, but their precise mechanisms of action and potential synergistic effects with chemotherapeutic drugs remain largely unexplored. This study aimed to elucidate the effects of AM extract on lung cancer cell line A549, confirm its apoptotic role, and investigate its combined impact with Docetaxel (DTX). The antiproliferative effects of AM on A549 cells were examined using the sulforhodamine B (SRB) assay, and the half-maximal inhibitory concentration (IC50) of AM alone and in combination with DTX was determined for 24, 48, and 72-hour periods. Combination indices were used to gauge the potential of this dual therapy. Results showed that AM inhibited the growth of A549 cells with IC50 1062.8, 580.2 and 307.9 μg/mL, for 24, 48 and 72 hours, respectively. Morphological observation showed that cells treated with AM would became smaller and more rounded, which are clear signs that apoptosis is taking place. Further investigation with Propidium Iodide staining revealed DNA condensation, evidence that apoptotic activity is occurring. Annexin V/7AAD double staining indicated that AM, especially in combination with DTX, triggered more Apoptosis in A549 cells. There was an increase in late apoptotic cells when AM was combined with DTX, indicating the synergism of both drugs. Furthermore, AM and the AM-DTX combination significantly increased reactive oxygen species activation in treated A549 cells. This suggests that AM alone and the combination with DTX promotes cell death in A549 cells. Notably, the AM-DTX combination ameliorated drug resistance and enhanced cytotoxicity against A549 cells. Our findings suggest that AM, particularly when used synergistically with DTX, could be a potential adjunctive therapeutic strategy for non-small cell lung cancer patients. Future research should aim to validate these results in vivo and in clinical trials. |
