Related Experiment Video

Updated: May 16, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Modulation of the PI3K/Akt signaling pathway by steroidal saponins: therapeutic implications in cancer

Mohammad Bagher Majnooni1, Maryam Naseri2, Shayan Bakhshy-Chenary2

  • 1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Frontiers in Pharmacology
|May 15, 2026
PubMed
Abstract

Insights

Steroidal saponins (SSs) show promise in targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway for cancer treatment, offering an alternative to conventional therapies. Further research is needed to overcome limitations for clinical application.

Area of Science:

  • Natural product chemistry
  • Molecular oncology
  • Pharmacology

Background:

  • The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway is crucial for cancer cell proliferation, survival, metastasis, and angiogenesis.
  • Conventional targeted therapies often face resistance, limiting their effectiveness against cancer.
  • Steroidal saponins (SSs) are natural compounds with recognized anticancer properties, targeting multiple cellular pathways.

Purpose of the Study:

  • To synthesize current evidence on how steroidal saponins (SSs) modulate the PI3K/Akt pathway for anticancer effects.
  • To outline translational opportunities and limitations for SSs in cancer therapy.

Main Methods:

  • A comprehensive review of preclinical and translational studies was conducted.
  • Studies indexed in PubMed, Scopus, and Google Scholar up to August 2025 were included.
  • Data on SSs modulating the PI3K/Akt/mTOR axis (in vitro, in vivo, ex vivo) were compiled and organized.

Main Results:

  • Steroidal saponins (SSs) demonstrate potential in targeting the PI3K/Akt pathway to combat cancer progression.
  • SSs induce apoptosis, inhibit metastasis and angiogenesis, and modulate the tumor microenvironment.
  • SSs can reverse multidrug resistance by modulating the PI3K/Akt pathway and enhance immune response.

Conclusions:

  • Emerging preclinical evidence supports combining SSs with chemotherapeutics for novel anticancer therapies.
  • Clinical development of SSs is hindered by low bioavailability, systemic toxicity, and lack of target specificity.
Keywords:
PI3K/AKT signalingangiogenesis inhibitionanticancer activityapoptosismultidrug resistancesteroidal saponins

More Related Videos

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...