Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system

Cheng Wei Tzeng, Wen Sheng Tzeng, Liang Tzung Lin, Chiang Wen Lee, Feng Lin Yen, Chun Ching Lin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Natural products offer great resources of developing new and effective chemopreventive or chemotherapeutic agents. Artocarpus communis extracts and its active constituent, prenylated flavonoid artocarpin induce human hepatocellular carcinoma cell death. However, the poor water solubility drawbacks of artocarpin restrict its clinical application and bioavailability. Purpose This study developed the artocarpin nanoparticle system to overcome the poor water solubility drawbacks and investigated the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. Methods Antiproliferative activity of artocarpin was evaluated by MTT assay. Cell morphology observation by microscope, DNA fragmentation assay, cell cycle analysis, Annexin V apoptosis cell staining, monodansylcadaverine and acridine orange staining and immunoblot analysis were used to evaluate the induction of autophagy by artocarpin. The determination of particle size, amorphous transformation, hydrogen-bond formation, yield, encapsulation efficiency and the solubility study were used to investigate the solubility enhancement mechanism of artocarpin. Results The present study demonstrates that the anticancer effect of artocarpin in HepG2 and PLC/PRF/5 hepatoma cells is mediated through the autophagic cell death mechanism. Results also demonstrated that artocarpin nanoparticles enhanced the solubility of artocarpin by reducing particle size, transforming high energy amorphous state, and forming hydrogen bond with excipients. Additionally, ArtN exhibited better autophagic cytotoxicity compared to free artocarpin. Conclusion This work reveals the antihepatoma activity of artocarpin by inducing autophagic cell death and the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. The research provided a basis of ArtN could be explored as a low-dose alternative of artocarpin in anticancer treatment and research applications.

Original languageEnglish
Pages (from-to)528-540
Number of pages13
JournalPhytomedicine
Volume23
Issue number5
DOIs
Publication statusPublished - May 15 2016

Fingerprint

Nanoparticles
Solubility
Hepatocellular Carcinoma
Autophagy
Particle Size
artocarpin lectin
Hydrogen
Artocarpus
Staining and Labeling
Acridine Orange
Water
Excipients
Annexin A5
DNA Fragmentation
Therapeutics
Liver Neoplasms
Biological Products
Research
Biological Availability
Cell Cycle

Keywords

  • Artocarpin
  • Autophagy
  • Hepatocellular carcinoma
  • Nanoparticle
  • Solubility

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine

Cite this

Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system. / Tzeng, Cheng Wei; Tzeng, Wen Sheng; Lin, Liang Tzung; Lee, Chiang Wen; Yen, Feng Lin; Lin, Chun Ching.

In: Phytomedicine, Vol. 23, No. 5, 15.05.2016, p. 528-540.

Research output: Contribution to journalArticle

Tzeng, Cheng Wei ; Tzeng, Wen Sheng ; Lin, Liang Tzung ; Lee, Chiang Wen ; Yen, Feng Lin ; Lin, Chun Ching. / Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system. In: Phytomedicine. 2016 ; Vol. 23, No. 5. pp. 528-540.
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AU - Lee, Chiang Wen

AU - Yen, Feng Lin

AU - Lin, Chun Ching

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AB - Background Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Natural products offer great resources of developing new and effective chemopreventive or chemotherapeutic agents. Artocarpus communis extracts and its active constituent, prenylated flavonoid artocarpin induce human hepatocellular carcinoma cell death. However, the poor water solubility drawbacks of artocarpin restrict its clinical application and bioavailability. Purpose This study developed the artocarpin nanoparticle system to overcome the poor water solubility drawbacks and investigated the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. Methods Antiproliferative activity of artocarpin was evaluated by MTT assay. Cell morphology observation by microscope, DNA fragmentation assay, cell cycle analysis, Annexin V apoptosis cell staining, monodansylcadaverine and acridine orange staining and immunoblot analysis were used to evaluate the induction of autophagy by artocarpin. The determination of particle size, amorphous transformation, hydrogen-bond formation, yield, encapsulation efficiency and the solubility study were used to investigate the solubility enhancement mechanism of artocarpin. Results The present study demonstrates that the anticancer effect of artocarpin in HepG2 and PLC/PRF/5 hepatoma cells is mediated through the autophagic cell death mechanism. Results also demonstrated that artocarpin nanoparticles enhanced the solubility of artocarpin by reducing particle size, transforming high energy amorphous state, and forming hydrogen bond with excipients. Additionally, ArtN exhibited better autophagic cytotoxicity compared to free artocarpin. Conclusion This work reveals the antihepatoma activity of artocarpin by inducing autophagic cell death and the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. The research provided a basis of ArtN could be explored as a low-dose alternative of artocarpin in anticancer treatment and research applications.

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KW - Autophagy

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KW - Nanoparticle

KW - Solubility

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