ArticleScientific reports2024
Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cells.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Piper nigrum Has an Antitumor Effect Through Regulation of the Phosphatidylinositol 3-Kinase Signaling Pathway in a Murine Model of Acute Myeloid Leukemia.Phytotherapy research : PTR · 2026Article
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Enhancing EGFR Inhibition: Monensin and Erlotinib Synergize to Eliminate Cancer Stem Cells in Canine Mammary Tumours.Veterinary and comparative oncology · 2026Article
- Natural Products as Modulators of the DNA Damage Response and Oncogenic Signaling in Breast Cancer Therapy.International journal of molecular sciences · 2026Review
- Role of Endogenous Myoglobin in Anthracycline Response in Breast Cancer.Biomolecules · 2026Article
- Mechanistic Insights into Piperine-Driven Oxidative Stress, Autophagy Activation and Anti-Migration Effects in Caco-2 Cells.Molecules (Basel, Switzerland) · 2026Article
- Metformin potentiates DSF/Cu-loaded pluronic nanoparticles to improve therapeutic efficacy in triple-negative breast cancer.BMC biotechnology · 2026Article
- Impact of cytosine and piperine on colorectal cancer progression based on Mendelian randomization and functional validation.Discover oncology · 2026Article
- Piperine protects ovarian follicles and stromal cells against doxorubicin-induced adverse effects in mouse ovaries.JBRA assisted reproduction · 2026Article
- Piperine as a modulator of cancer hallmarks: mechanistic insights and therapeutic potential.Frontiers in oncology · 2026Review
- Anticancer effect of piperine, a black pepper compound, regulating apoptosis mediated through extracellular vesicles and cathepsin D in acute leukemia.Scientific reports · 2025Article
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- HJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models.Scientific reports · 2025Article
- Unlocking the full potential of piperine-loaded nanocarriers for cancer treatment.Therapeutic delivery · 2025Review
- Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.Cancer biology & medicine · 2025Review
- Evaluating the Cytotoxic Potential of 3-(2-(3,4 dimethoxyphenyl)-2-oxoethylidene) indolin-2-one) (RAJI) on Triple Negative Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- The Hidden Power of Black Pepper: Exploring Piperine's Role in Cancer.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Review
- Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.World journal of clinical oncology · 2025Review
- Mitigating Doxorubicin-Induced Cardiotoxicity and Enhancing Anti-Tumor Efficacy with a Metformin-Integrated Self-Assembled Nanomedicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.International journal of molecular sciences · 2025Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway's negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.
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