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Antiproliferative Effects of Free and Encapsulated Hypericum Perforatum L. Extract and Its Potential Interaction with Doxorubicin for Esophageal Squamous Cell Carcinoma

  • Amjadi, Issa ;
  • Mohajeri, Mohammad ;
  • Borisov, Andrei ;
  • Hosseini, Motahare-Sadat
  • Received : 2017.11.14
  • Accepted : 2019.05.20
  • Published : 2019.06.28

Abstract

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

Keywords

doxorubicin;hypericum perforatum extract;nanoparticles;esophageal squamous cell carcinoma;drug resistance

DHOCBS_2019_v22n2_102_f0002.png 이미지

Figure 1 Effects of Dox and HP extract on KYSE-30 and normal cells: (A) cytotoxicity of Dox in KYSE-30 cells; (B) cytotoxicity of Dox NPs in KYSE-30 cells; (C) cytotoxicity of HP extract in KYSE-30 cells; (D) cytotoxicity of HP NPs in KYSE-30 cells; (E) cytotoxicity of Dox NPs in normal cells; (F) cytotoxicity of HP NPs in normal cells. MAP: mean arterial pressure; SBP: systolic blood pressure; HR: heart rate

DHOCBS_2019_v22n2_102_f0002.png 이미지

Figure 1 Effects of Dox and HP extract on KYSE-30 and normal cells: (A) cytotoxicity of Dox in KYSE-30 cells; (B) cytotoxicity of Dox NPs in KYSE-30 cells; (C) cytotoxicity of HP extract in KYSE-30 cells; (D) cytotoxicity of HP NPs in KYSE-30 cells; (E) cytotoxicity of Dox NPs in normal cells; (F) cytotoxicity of HP NPs in normal cells. MAP: mean arterial pressure; SBP: systolic blood pressure; HR: heart rate

DHOCBS_2019_v22n2_102_f0003.png 이미지

Figure 2 Expression of cyclin D1 in the cancer cells treated with the seven samples [S1 (Dox), S2 (Dox NPs), S3 (HP extract), S4 (HP NPs), S5 (Dox and HP extract), S6 (Dox and HP NPs) and S7 (HP extract and Dox NPs)], and in normal cells treated with the two samples [S8 (Dox NPs) and S9 (HP NPs)].

DHOCBS_2019_v22n2_102_f0003.png 이미지

Figure 2 Expression of cyclin D1 in the cancer cells treated with the seven samples [S1 (Dox), S2 (Dox NPs), S3 (HP extract), S4 (HP NPs), S5 (Dox and HP extract), S6 (Dox and HP NPs) and S7 (HP extract and Dox NPs)], and in normal cells treated with the two samples [S8 (Dox NPs) and S9 (HP NPs)].

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