Colorectal cancer (CRC) is the third most prevalent cancer globally, with limited effective treatment options and significant chemotherapy resistance. Saikosaponin A (SSA), a triterpenoid saponin from Radix Bupleuri, exhibits anti-inflammatory and antitumor properties, but its mechanism of action in CRC remains undefined. This study aims to investigate SSA's antitumor effects against HCT116 CRC cells and elucidate the underlying molecular mechanisms through integrated omics analysis and functional validation. SSA selectively inhibited HCT116 proliferation and colony formation with minimal toxicity to HEK293 cells. SSA suppressed xenograft tumor growth by 54% (10 mg/kg) without affecting body weight or organ histology. Integrated omics revealed 6,033 DEGs and 39 DEMs, with 81 genes and 37 miRNAs significantly enriched in the MAPK pathway. SSA induced apoptosis in a dose-dependent manner, increasing ROS production 3.2-fold and decreasing MMP. Mechanistically, SSA activated p38 and JNK MAPK pathways, upregulated CHOP-mediated ER stress, and modulated apoptosis proteins (decreased Bcl-2, increased cleaved caspase-3 and -9). Network analysis identified miR-132-3p as a key regulator of MAPK hub genes (KRAS, SOS1, BRAF). SSA exerts potent antitumor activity against HCT116 CRC cells, representing a promising therapeutic candidate for CRC treatment.

With an aim to comprehend the precise regulatory mechanism of dioscin against endometrial carcinoma (EC), we firstly extracted the components from Polygonatum sibiricum followed by identification and structural characterization. The anti-EC activity of dioscin was initially determined based on the inhibition of Ishikawa cell proliferation and tumor growth. The high-throughput sequencing data indicated that dioscin not only promoted apoptosis, including decrease of poly ADP-ribose polymerase (PARP) and B-cell lymphoma-2 (Bcl-2) and increase of c-PARP and Bcl-2-associcated agonist of cell death (Bad), but also induced autophagy, including increase of autophagic lysosomes and LC3Ⅱ/LC3Ⅰ ratio. Mechanistic exploration suggested that dioscin induced autophagy and apoptosis through inhibition of PI3K/AKT/mTOR signaling pathway. Besides, the dioscin-regulated p53 pathway was mainly involved in autophagy induction. Furthermore, inhibition of Ishikawa cell autophagy was linked to dioscin-induced apoptosis. Our data suggest the immense potential of dioscin for the development of functional food for EC and related medical application.

To explore the function of licochalcone A as an anticancer phytochemical on HepG2 cells and investigate its potential mechanisms, we analyzed the microRNAs (miRNAs) expression profile of HepG2 cells in response to licochalcone A (70 μmol/L) in vitro. 102 dysregulated miRNAs were detected, and SP1 was expected as the transcription factor that regulates the functions of most screened miRNAs. A sum of 431 targets, the overlap of predicted mRNAs from TargetScan, miRDB, and miRtarbase were detected as the targets for these dysregulated miRNAs. FoxO signaling pathway was the hub pathway for the targets. A protein-protein interaction network was structured on the STRING platform to discover the hub genes. Among them, PIK3R1, CDC42, ESR1, SMAD4, SUMO1, KRAS, AGO1, etc. were screened out. Afterwards, the miRNA-target networks were established to screen key dysregulated miRNAs. Two key miRNAs (hsa-miR-133b and hsa-miR-145-5p) were filtered. Finally, the miRNA-target-transcription factor networks were constructed for these key miRNAs. The networks for these key miRNAs included three and two transcription factors, respectively. These identified miRNAs, transcription factors, targets, and regulatory networks may offer hints to understand the molecular mechanism of licochalcone A as a natural anticarcinogen.