Curcumol β-cyclodextrin inclusion complex enhances radiosensitivity of esophageal cancer under hypoxic and normoxic condition
Description
Headings Ethnopharmacological relevance: The genus Curcuma is in the family Zingiberaceae. Curcuma, as a traditional medicine, has been widely used for anti-cancer, anti-hepatic fibrosis, anti-fungal, anti-viral, and anti-inflammatory. Curcumol, as an important active component of Curcuma, extracts from numerous plants of family Zingiberaceae, has been reported to have antitumor activity in various types of human tumor cells. β-cyclodextrin, as a stabilizing agent, greatly increases the stability and solubility of curcumol. And curcumol β-cyclodextrin inclusion complex (CβC) has been proved to retain obvious antitumor activity. Nevertheless, its radiosensitization effect on esophageal cancer (EC) has not been reported yet. Aim of the study: Radiotherapy is an indispensable treatment for EC, but radioresistance is not uncommon. Based on this consideration, the aim of this study was to identify whether CβC is a potential radiosensitizer for EC cells under hypoxic and normoxic condition. Materials and Methods: In the present study, curcumol was prepared as an inclusion complex with β-cyclodextrin. EC cell lines (TE-1 and ECA109) were incubated under hypoxia or normoxia, and treated with radiation and CβC. 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. Conclusions: 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.