2. Academic Validation
  3. Naturally Occurring Bicoumarin Compound Daphnoretin Inhibits Growth and Induces Megakaryocytic Differentiation in Human Chronic Myeloid Leukemia Cells

Naturally Occurring Bicoumarin Compound Daphnoretin Inhibits Growth and Induces Megakaryocytic Differentiation in Human Chronic Myeloid Leukemia Cells

  • Cells. 2022 Oct 16;11(20):3252. doi: 10.3390/cells11203252.
Yu-Chuen Huang 1 2,  Chun-Ping Huang 1 3,  Chin-Ping Lin 4,  Kai-Chien Yang 4,  Yu-Jie Lei 2,  Hao-Pei Wang 1 5,  Yueh-Hsiung Kuo 2 6 7,  Yu-Jen Chen 2 4 8 9
Affiliations

Affiliations

  • 1 School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
  • 2 Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan.
  • 3 Integration Center of Traditional Chinese and Modern Medicine, Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien 97002, Taiwan.
  • 4 Department of Medical Research, MacKay Memorial Hospital, New Taipei City 25160, Taiwan.
  • 5 Department of Public Health, China Medical University, Taichung 40402, Taiwan.
  • 6 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan.
  • 7 Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
  • 8 Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 10449, Taiwan.
  • 9 Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan.
PMID: 36291120 DOI: 10.3390/cells11203252
Abstract

Daphnoretin extracted from the stem and roots of Wikstroemia indica (L.) C.A. Mey has been shown to possess Antiviral and antitumor activities. Herein, we hypothesized that daphnoretin might induce megakaryocytic differentiation, thereby inhibiting the proliferation of cells and serving as a differentiation therapy agent for chronic myeloid leukemia (CML). Daphnoretin-treated K562 and HEL cells were examined for growth inhibition, cell morphology, and megakaryocyte-specific markers. Potential mechanisms of megakaryocytic differentiation of daphnoretin-treated K562 cells were evaluated. The results showed that daphnoretin inhibited the growth of K562 and HEL cells in a dose- and time-dependent manner. Flow cytometry analyses revealed that daphnoretin treatment slightly increased the proportion of sub-G1 and polyploid cells compared to that of dimethyl sulfoxide (DMSO)-treated control cells. Morphological examination showed that daphnoretin-treated K562 and HEL cells exhibited enlarged contours and multinucleation as megakaryocytic characteristics compared to DMSO-treated control cells. Daphnoretin treatment also dramatically enhanced the expression of megakaryocytic markers CD61 and CD41. Under optimal megakaryocytic differentiation conditions, daphnoretin increased the phosphorylation of STAT3 but not STAT5. In summary, daphnoretin inhibited cell growth and induced megakaryocytic differentiation in K562 and HEL cells. The efficacy of daphnoretin in vivo and in patients with CML may need further investigations for validation.

Keywords

daphnoretin; differentiation; megakaryocyte; myeloid leukemia; protein kinase C.

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