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Abstract
Background Lung and liver cancer rank among the most prevalent malignancies affecting global health. While herbs are extensively utilized in Traditional Chinese Medicine (TCM) for cancer treatment, the mechanisms behind these herbs remain largely unknown.
Methods We treated A549 and Huh7 cells with extracts from 14 different Chinese herbs. Herbs which showed significant efficacy in reducing cancer cell viability were selected for RNA sequencing. Bio-informatics analysis including differential gene expression, gene set functional, transcription factor prediction and similar compound recognition using LINCS database were performed to reveal the mechanisms underlying their therapeutic effects, followed by experimental validation (figure 1).
Results Pulsatilla chinensis showed the best anticancer potency in A549 and Huh7 cells among 14 herbs tested, followed by Bupleurum chinense, and Polyporus umbellatus. We observed different mechanisms of anti-cancer action in A549 and Huh7 cells induced by P. chinensis treatment. Our integrative approach, combining transcriptomic data and experimental validation, has revealed that P. chinensis exhibits anti-cancer properties by inducing apoptosis through regulating the p53-MDM2 and TNF-α/NF-κB pathways in A549 and Huh7 cells, respectively. Using our own designed algorithm based on the LINCS L1000 database, We identified two drugs, AMG232 and Nutlin-3, that had treatment effects similar to P. chinensis in A549 cells. Both drugs are inhibitors of the MDM2-p53 interaction. Besides, western blot analysis revealed elevated levels of apoptotic proteins, including cleaved PARP, active caspase-3, active caspase-8, P53, and MDM2, in A549 cells treated with P. chinensis. Interestingly, an increase in MDM2 protein levels was not observed in Huh7 cells, indicating that P. chinensis induces MDM2-p53-related apoptotic cell death specifically in A549 cells. Besides, we found that although P. chinensis affected different pathways in A549 and Huh7 cells, the triggered transcriptional factors were similar and they were associated with the cell cycle regulation.
Conclusions We conclude that P. chinensis has a significant anticancer effect on both A549 and Huh7 cells, signifying its potential for clinical translation in cancer treatment after additional preclinical and clinical studies.
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