Curcumol β-cyclodextrin inclusion complex enhances radiosensitivity of esophageal cancer under hypoxic and normoxic condition

Jpn J Radiol. 2023 Nov;41(11):1275-1289. doi: 10.1007/s11604-023-01446-7. Epub 2023 May 25.

Abstract

Purpose: Radiotherapy is an indispensable treatment for esophageal cancer (EC), but radioresistance is not uncommon. Curcumol, as an active extract from traditional Chinese medicines, has been reported to have antitumor activity in various types of human tumor cells. However, its reversal of radioresistance has been rarely reported.

Materials and methods: In the present study, curcumol was prepared as an inclusion complex with β-cyclodextrin. EC cell lines were treated with radiation and curcumol β-cyclodextrin inclusion complex (CβC), and the effect of radiosensitization of CβC was investigated in vitro and in vivo. The in vitro experiments included cell proliferation assay, clonogenic survival assay, apoptosis assay, cell cycle assay, and western blot assay.

Results: The in vitro data revealed that CβC and irradiation synergistically inhibited the proliferation, reduced the colony formation, promoted the apoptosis, increased the G2/M phase, inhibited DNA damage repair, and reversed the hypoxia-mediated radioresistance of EC cells to a greater extent than did CβC alone or irradiation alone. The sensitization enhancement ratios (SERs) were 1.39 for TE-1 and 1.48 for ECA109 under hypoxia. The SERs were 1.25 for TE-1 and 1.32 for ECA109 under normoxia. The in vivo data demonstrated that the combination of CβC and irradiation could inhibit tumor growth to the greatest extent compared with either monotherapy alone. The enhancement factor was 2.45.

Conclusion: This study demonstrated that CβC could enhance radiosensitivity of EC cells under hypoxic and normoxic condition. Thus, CβC can be used as an effective radiosensitizer for EC.

Keywords: Apoptosis; Cell cycle; Curcumol; Esophageal cancer; Radiosensitivity.

MeSH terms

  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / radiotherapy
  • Humans
  • Hypoxia
  • Radiation Tolerance / genetics
  • beta-Cyclodextrins* / pharmacology

Substances

  • curcumol
  • beta-Cyclodextrins