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Andrographolide and its potent derivative exhibit anticancer effects against imatinib-resistant chronic myeloid

Hsin-Chia Liao1, Yi-Ju Chou2, Ching-Cheng Lin1

  • 1Institute of Traditional Medicine, National Yang-Ming University, Taipei 11221, Taiwan.

Biochemical Pharmacology
|March 2, 2019
PubMed

Insights

Andrographolide and NCTU-322 show promise for treating chronic myelogenous leukemia (CML). These compounds target the Bcr-Abl oncoprotein in both imatinib-sensitive and resistant CML cells, offering a new therapeutic avenue.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Chronic myelogenous leukemia (CML) is primarily treated with imatinib, targeting the Bcr-Abl oncoprotein.
  • Imatinib resistance is a significant clinical challenge in CML treatment.
  • Andrographolide, from Andrographis paniculata, exhibits known anticancer properties.

Purpose of the Study:

  • To investigate the therapeutic potential of andrographolide and its derivative NCTU-322 against imatinib-sensitive and resistant CML.
  • To elucidate the mechanism of action of andrographolide and NCTU-322 in CML cells.

Main Methods:

  • Treatment of human CML cell lines (imatinib-sensitive and resistant) with andrographolide and NCTU-322.
  • Analysis of Bcr-Abl oncoprotein levels and Hsp90-dependent mechanisms.
  • Assessment of cytotoxicity, differentiation, mitotic arrest, and apoptosis induction.
  • In vivo studies to evaluate anticancer activity in imatinib-resistant CML models.

Main Results:

  • Both andrographolide and NCTU-322 downregulated Bcr-Abl in resistant CML cells via an Hsp90-dependent pathway.
  • NCTU-322 demonstrated superior efficacy over andrographolide in Bcr-Abl downregulation, Hsp90 cleavage, and cytotoxicity.
  • Both compounds induced differentiation, mitotic arrest, and apoptosis in sensitive and resistant CML cells.
  • NCTU-322 exhibited significant in vivo anticancer activity against imatinib-resistant CML.

Conclusions:

  • Andrographolide and NCTU-322 inhibit Bcr-Abl function through a distinct mechanism compared to imatinib.
  • These compounds induce multiple anticancer effects, including differentiation, mitotic arrest, and apoptosis.
  • Andrographolide and NCTU-322 represent potential therapeutic agents for both imatinib-sensitive and resistant CML.
Keywords:
AndrographolideBcr-AblChronic myelogenous leukemiaDrug resistanceImatinib

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