Modulation of apoptosis-related cell signalling pathways by curcumin as a strategy to inhibit tumor progression

Mol Biol Rep. 2014 Jul;41(7):4583-94. doi: 10.1007/s11033-014-3329-9. Epub 2014 Mar 7.


A hallmark of cancer is resistance to apoptosis, with both the loss of proapoptotic signals and the gain of anti-apoptotic mechanisms contributing to tumorigenesis. As inducing apoptosis in malignant cells is one of the most challenging tasks regarding cancer, researchers increasingly focus on natural products to regulate apoptotic signaling pathways. Curcumin, a polyphenolic derivative of turmeric, is a natural compound derived from Curcuma longa, has attracted great interest in the research of cancer during the last half century. Extensive studies revealed that curcumin has chemopreventive properties, which are mainly due to its ability to arrest cell cycle and to induce apoptosis in cancer cells either alone or in combination with chemotherapeutic agents or radiation. The underlying action mechanisms of curcumin are diverse and has not been elucidated so far. By regulating multiple important cellular signalling pathways including NF-κB, TRAIL, PI3 K/Akt, JAK/STAT, Notch-1, JNK, etc., curcumin are known to activate cell death signals and induce apoptosis in pre-cancerous or cancer cells without affecting normal cells, thereby inhibiting tumor progression. Several phase I and phase II clinical trials indicate that curcumin is quite safe and may exhibit therapeutic efficacy. This article reviews the main effects of curcumin on the different apoptotic signaling pathways involved in curcumin induced apoptosis in cancer cells via cellular transduction pathways and provides an in depth assessment of its pharmacological activity in the management of tumor progression.

MeSH terms

  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Tumor
  • Clinical Trials as Topic
  • Curcumin / therapeutic use*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism


  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • NF-kappa B
  • STAT Transcription Factors
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Proto-Oncogene Proteins c-akt
  • Curcumin