# Induction of Extrinsic Apoptotic Pathway in Pancreatic Cancer Cells by Apteranthes europaea Root Extract

**Authors:** Rinat Bar-Shalom, Lana Abdelhak, Wafa Zennouhi, Farid Khallouki, Laila Benbacer, Fuad Fares

PMC · DOI: 10.3390/ijms262010221 · International Journal of Molecular Sciences · 2025-10-21

## TL;DR

This study shows that a root extract from Apteranthes europaea can trigger cell death in pancreatic cancer cells through the extrinsic apoptotic pathway.

## Contribution

The novel finding is that A. europaea root extract induces apoptosis via the extrinsic pathway in pancreatic cancer cells.

## Key findings

- A. europaea root extract reduced pancreatic cancer cell proliferation and induced apoptosis.
- Caspase-8 was activated, while caspase-9 remained inactive, indicating extrinsic apoptosis.
- Cleavage of caspase-3 and PARP confirmed apoptosis induction.

## Abstract

Pancreatic cancer is an extremely deadly disease with few effective treatment options and the lowest survival rate among all types of cancer. As a result, there is an urgent need for the development of new and more effective treatment strategies. Natural products have long been a vital source of drug discovery, offering unique bioactive compounds, and representing a promising source for new, effective, and less toxic treatments. In the present study, we aimed to investigate the effects of Apteranthes europaea (Guss.) Murb (A. europaea) root extract on the growth of pancreatic cancer cells. The proliferation assay (XTT) and real-time analysis using the IncuCyte Live-Cell Analysis System, following treatment of PL45 and Mia PaCa-2 pancreatic cancer cells with escalating concentrations (50–200 µL) to A. europaea root extract, demonstrated the progression of apoptosis. Apoptosis induction was confirmed through cell cycle analysis and Annexin V/PI double staining assays. Western blot analysis revealed the distinct activation of caspase-8, accompanied by the cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Interestingly, no activation of caspase-9 was observed, suggesting the involvement of the extrinsic apoptotic pathway. Our findings suggest that A. europaea extract may be a potential novel strategy for treating pancreatic cancer.

## Linked entities

- **Proteins:** casp8 (caspase 8, apoptosis-related cysteine peptidase), Casp3 (caspase 3), PARP2 (poly(ADP-ribose) polymerase), PARP1 (poly(ADP-ribose) polymerase 1), Casp9 (caspase 9)
- **Diseases:** pancreatic cancer (MONDO:0005192)

## Full-text entities

- **Genes:** CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}
- **Diseases:** cancer (MESH:D009369), Pancreatic Cancer (MESH:D010190)
- **Chemicals:** PI (MESH:D010716), A. europaea extract (-)
- **Species:** Caralluma europaea (species) [taxon 197236]
- **Cell lines:** PL45 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_3567), Mia PaCa-2 — Homo sapiens (Human), Pancreatic carcinoma, Cancer cell line (CVCL_4011)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12565304/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12565304/full.md

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Source: https://tomesphere.com/paper/PMC12565304