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Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways

Zhi Lan Guo1,2, Jing Zhe Li2, Yan Yan Ma2

  • 1College of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, China.

BMC Cell Biology
|December 31, 2018
PubMed
Abstract

Insights

Shikonin, a natural compound, sensitizes cancer cells resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy. This combination enhances TRAIL

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • TRAIL is a promising antitumor agent due to its selective cancer cell toxicity.
  • Cancer cells can develop resistance to TRAIL-induced apoptosis, limiting its therapeutic efficacy.
  • Novel agents are required to overcome TRAIL resistance and enhance its antitumor effects.

Purpose of the Study:

  • To investigate the potential of shikonin, a natural compound, in sensitizing TRAIL-resistant cancer cells.
  • To elucidate the molecular mechanisms underlying shikonin's sensitizing effects on TRAIL-induced cytotoxicity.

Main Methods:

  • Treatment of TRAIL-resistant A549 cancer cells with shikonin and TRAIL.
  • Analysis of cell viability and apoptosis.
  • Examination of key signaling pathways (caspase, JNK, STAT3, AKT) and protein expression levels (Mcl-1, Bcl-2, Bcl-xL, c-FLIP, XIAP, Bid).

Main Results:

  • Shikonin significantly decreased the viability of TRAIL-resistant A549 cells when combined with TRAIL.
  • Combined treatment activated caspase and JNK pathways.
  • Inhibited STAT3 and AKT pathways, downregulated antiapoptotic proteins (Mcl-1, Bcl-2, Bcl-xL, c-FLIP, XIAP), and upregulated proapoptotic Bid.

Conclusions:

  • Shikonin effectively sensitizes TRAIL-resistant cancer cells to TRAIL-induced cytotoxicity.
  • The sensitization mechanism involves modulation of JNK, STAT3, and AKT pathways.
  • Shikonin alters the balance of pro- and antiapoptotic proteins, promoting cancer cell death.
Keywords:
Resistant cancersSensitizationShikoninTRAIL

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