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Article

Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways

  • Authors:
    • Xiaodie Cao
    • Chong Ma
    • Xin Wang
    • Cui Wang
    • Lanlin Shen
    • Jingru Wei
    • Rongmin Yang
    • Yan Li
    • Xu He
    • Li Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, School of Basic Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China, The First People's Hospital of Yunnan Province, Kunming University of Science and Technology Affiliated Hospital, Kunming, Yunnan 650032, P.R. China
  • Article Number: 298
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    Published online on: May 18, 2026
       https://doi.org/10.3892/ol.2026.15653
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Abstract

Non‑small cell lung cancer (NSCLC) remains a major health challenge due to its poor prognosis and low 5‑year survival rate; therefore, the development of efficient and less toxic anti‑NSCLC therapies is of great importance. The present study aimed to investigate the anti‑survival and pro‑apoptotic effects of Jaceosidin, a flavonoid, on human NSCLC cells and to uncover its underlying mechanism. Cell viability, cell cycle progression and apoptosis were assess using the MTS assay and flow cytometry, and protein expression was analyzed by western blot analysis. The results showed that Jaceosidin significantly reduced A549 cell viability in a dose‑dependent manner, whereas it exhibited significantly lower cytotoxicity against 293T cells. In addition, cell cycle distribution analysis demonstrated that A549 cell treatment with Jaceosidin induced S‑phase cell cycle arrest, which was accompanied by p21 upregulation. Jaceosidin also enhanced cell apoptosis, and upregulated cleaved‑poly‑ADP ribose polymerase and cleaved‑caspase‑3 expression in a dose‑dependent manner. Furthermore, Jaceosidin promoted the release of cytochrome c (cyto‑c) from mitochondria into the cytoplasm, as detected by digitonin‑based fractionation and western blotting, thus resulting in increased cytosolic cyto‑c levels. Finally, Jaceosidin significantly reduced the expression of Ras and Raf, and the downstream signaling molecules ERK1/2 and Akt, which may suppress A549 cell viability and enhance apoptosis. Overall, the current study suggested that Jaceosidin exerts potential anti‑NSCLC activity with tumor‑selective cytotoxicity through inhibiting the Ras/Raf/MEK/ERK and Akt pathways, and activating both intrinsic mitochondrial and extrinsic apoptotic pathways, thus representing a promising natural product candidate for future NSCLC therapy.
View Figures

Figure 1

Jaceosidin inhibits viability and
induces S-phase arrest in A549 cells. (A) Chemical structure of
Jaceosidin. Viability of (B) A549 and (C) 293T cells treated with
increasing concentrations of Jaceosidin for 72 h was assessed using
MTS assay. (D) Flow cytometric analysis was performed to determine
the cell cycle distribution of A549 cells treated with increasing
concentrations of Jaceosidin for 24 h. As labelled directly on the
histograms, the 2n and 4n labels mark the DNA content corresponding
to the G0/G1 (diploid) and G2/M
(tetraploid) phases, respectively. Data are presented as the mean ±
SD of three independent experiments (n=3). Statistical differences
were analyzed by one-way ANOVA followed by Tukey's post hoc test.
**P<0.01, ***P<0.001 vs. control.

Figure 2

Jaceosidin induces apoptosis in A549
cells. (A) Annexin V-FITC/PI double staining was performed to
detect apoptosis in A549 cells treated with Jaceosidin for 24 h.
(B) Expression levels of the apoptosis-related proteins PARP and
caspase-3 were detected in A549 cells treated with increasing
concentrations of Jaceosidin for 24 h, or with 120 µM Jaceosidin
for the indicated times, by western blot analysis. (C) Statistical
analysis of apoptosis rates. (D) Semi-quantification of relative
protein levels of PARP, cleaved-PARP, caspase-3 and
cleaved-caspase-3. Data are presented as the mean ± SD of three
independent experiments (n=3). Statistical differences were
analyzed by one-way ANOVA followed by Tukey's post hoc test.
*P<0.05, **P<0.01, ***P<0.001 vs. control. ns, not
significant; PARP, poly-ADP ribose polymerase; PI, propidium
iodide.

Figure 3

Effects of Jaceosidin on
apoptosis-related signaling proteins and the cell cycle regulator
p21. (A) Western blot analysis was performed to detect the
expression levels of the apoptosis-related proteins caspase-8,
cleaved-caspase-8, caspase-9, cleaved-caspase-9, Bcl-2 and Bax in
A549 cells treated with the indicated concentrations of Jaceosidin
for 36 h, or with 120 µM Jaceosidin for the indicated time points.
(B) Western blot analysis was carried out to determine the
expression levels of cyto-c in cytosolic fractions of A549 cells
treated with the same concentrations of Jaceosidin. Western blot
analysis of p21 was also performed under identical treatment
conditions. (C) Densitometric analysis of caspase-8,
cleaved-caspase-8, caspase-9, cleaved-caspase-9, Bcl-2, Bax, cyto-c
and p21. Data are presented as the mean ± SD of three independent
experiments (n=3). Statistical differences were analyzed by one-way
ANOVA followed by Tukey's post hoc test. *P<0.05, **P<0.01,
***P<0.001 vs. control. Cyto-c, cytochrome c; ns, not
significant.

Figure 4

Jaceosidin inhibits MAPK
(Ras/Raf/MEK/ERK) and Akt signaling pathways in A549 cells. (A)
Western blot analysis of Ras, Raf, ERK1/2 and Akt in A549 cells
treated with the indicated concentrations of Jaceosidin for 36 h,
or treated with 120 µM Jaceosidin for the indicated time points.
(B) Densitometric analysis of Ras and Raf. (C) Densitometric
analysis of p-ERK1/2, ERK1/2, p-Akt and Akt. Data are presented as
the mean ± SD of three independent experiments (n=3). Statistical
differences were analyzed by one-way ANOVA followed by Tukey's post
hoc test. *P<0.05, **P<0.01, ***P<0.001 vs. control. ns,
not significant; p-, phosphorylated.

Figure 5

Proposed molecular mechanism of
Jaceosidin-mediated inhibition of viability and induction of
apoptosis in non-small cell lung cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Cao X, Ma C, Wang X, Wang C, Shen L, Wei J, Yang R, Li Y, He X, Chen L, Chen L, et al: Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways. Oncol Lett 32: 298, 2026.
APA
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J. ... Chen, L. (2026). Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways. Oncology Letters, 32, 298. https://doi.org/10.3892/ol.2026.15653
MLA
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J., Yang, R., Li, Y., He, X., Chen, L."Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways". Oncology Letters 32.1 (2026): 298.
Chicago
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J., Yang, R., Li, Y., He, X., Chen, L."Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways". Oncology Letters 32, no. 1 (2026): 298. https://doi.org/10.3892/ol.2026.15653
Copy and paste a formatted citation
x
Spandidos Publications style
Cao X, Ma C, Wang X, Wang C, Shen L, Wei J, Yang R, Li Y, He X, Chen L, Chen L, et al: Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways. Oncol Lett 32: 298, 2026.
APA
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J. ... Chen, L. (2026). Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways. Oncology Letters, 32, 298. https://doi.org/10.3892/ol.2026.15653
MLA
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J., Yang, R., Li, Y., He, X., Chen, L."Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways". Oncology Letters 32.1 (2026): 298.
Chicago
Cao, X., Ma, C., Wang, X., Wang, C., Shen, L., Wei, J., Yang, R., Li, Y., He, X., Chen, L."Jaceosidin inhibits cell viability and induces apoptosis in non‑small cell lung cancer by inhibiting the Ras/Raf/MEK/ERK and Akt pathways". Oncology Letters 32, no. 1 (2026): 298. https://doi.org/10.3892/ol.2026.15653
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