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Medicago sativa Extracts Enhance the Anticancer Efficacy of GEM in PANC-1 Cells through Apoptosis Induction and

Nazanin Jamshidi1, Negar Jamshidi1, Mohammad Zaman2

  • 1Kimia Andisheh Teb, Medical and Molecular Laboratory Research Co., Tehran, Iran.

Asian Pacific Journal of Cancer Prevention : APJCP
|May 29, 2025
PubMed
Abstract

Insights

This study shows that combining M. sativa ethanol extract with Gemcitabine (GEM) enhances pancreatic cancer cell death. This natural product combination therapy offers a promising approach for treating pancreatic cancer.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Products Chemistry

Background:

  • Pancreatic cancer (PC) presents a significant clinical challenge due to its poor prognosis and limited therapeutic options.
  • Combinatorial therapies, particularly those incorporating natural products, are being explored to improve efficacy and reduce side effects.
  • This research investigates the potential of Medicago sativa (M. sativa) as an adjunct to Gemcitabine (GEM) chemotherapy for PANC-1 pancreatic cancer cells.

Purpose of the Study:

  • To evaluate the anticancer properties of M. sativa extracts.
  • To determine if M. sativa can sensitize PANC-1 cells to Gemcitabine (GEM).
  • To assess the safety of M. sativa and GEM combination therapy on normal cells.

Main Methods:

  • Assessed antioxidant activity and total phenolic content of M. sativa extracts using DPPH and spectrophotometric assays.
  • Evaluated cytotoxicity of extracts and GEM on PANC-1 and HUVEC cells via MTT assay.
  • Analyzed apoptosis induction using flow cytometry, DNA fragmentation assays, and Western blot/qRT-PCR for apoptosis-related gene expression (Bcl-2, Bax, CASP3).

Main Results:

  • M. sativa water extract showed the highest total phenolic content.
  • The combination of M. sativa EtOH extract and GEM demonstrated enhanced cytotoxicity against PANC-1 cells compared to GEM alone, with no observed toxicity in HUVEC cells.
  • Combination therapy significantly increased apoptosis rates and induced characteristic apoptotic cell death markers, including DNA fragmentation and altered expression of Bcl-2, Bax, and CASP3.

Conclusions:

  • M. sativa ethanol extract shows potential as a sensitizing agent for pancreatic cancer chemotherapy.
  • The combination of M. sativa EtOH extract with Gemcitabine (GEM) presents a promising adjunctive therapeutic strategy for pancreatic cancer.
  • Further research into this natural product-based combinatorial approach is warranted for pancreatic cancer treatment.
Keywords:
ApoptosisCombination therapyGEMMedicago sativaPC

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