Prostate cancer (PCa)
often progresses to castration-
resistant prostate cancer (CRPC),
which is linked to higher treatment
resistance and recurrence rates.
This highlights the urgent need for
new therapeutic options. Natural
products, especially flavonoids,
have shown promise in reducing
drug resistance and possess both
antioxidant and anticancer effects.
Developing drugs that specifically
target CRPC could offer significant
therapeutic advantages.
Methods: Chrysosplenetin B (CspB)
was extracted and purified from the herb Laggera pterodonta (DC.) Benth. using traditional
flavonoid extraction techniques, followed by high-performance liquid chromatography (HPLC)
for purity assessment and nuclear magnetic resonance (NMR) for structural identification. The
effect of CspB on the viability of PCa cells was evaluated using the Cell Counting Kit-8 assay.
Subsequently, transcriptome analysis was conducted, and cell cycle progression was assessed
through flow cytometry in conjunction with propidium iodide (PI) staining. Additionally, western
blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to
confirm the expression levels of relevant proteins and genes.
Results: CspB was found to inhibit the proliferation of PC3, DU145, and LNCaP cells in a dose-
dependent manner, with a stronger effect noted in PC3 and DU145 cells. Transcriptomic analysis
revealed that CspB treatment led to cell cycle arrest, particularly in PC3 cells. Flow cytometry
with PI staining confirmed that CspB caused G1 phase cell cycle arrest in PC3 cells. Moreover,
CspB treatment significantly increased the expression of essential members of the Cip/Kip family,
including CIP1/P21 and KIP1/P27, as well as CDKN2B (P15) and CDKN2D (P19) from the
INK4 family. Additionally, CspB exposure notably raised the expression of the G1 phase-negative
regulatory gene CDKN1C, while key cell cycle regulators like CDK6 and E2F1 were significantly
downregulated at the protein level.
Conclusion: Our findings indicate that CspB effectively inhibits the proliferation of CRPC cells by
reducing the activity of cell cycle proteins and cyclin-dependent kinase (CDK) complexes while
upregulating the expression of P21 and P27 and inducing G1 phase cell cycle arrest. These results
highlight the potential of CspB as a promising candidate for developing therapeutic agents aimed
at targeting CRPC.
