Fanghua Qiu, Lifang Liu, Yu Lin, Zetian Yang and Feng Qiu* Pages 1021 - 1028 ( 8 )
Background: Esophageal squamous cell carcinoma (ESCC), the most prevalent histologic subtype of esophageal cancer, is an aggressive malignancy with poor prognosis and a high incidence in the East. Corilagin, an active component present in Phyllanthus niruri L., has been shown to suppress tumor growth in various cancers. However, the effects of corilagin on ESCC and the mechanisms for its tumor suppressive function remain unknown.
Methods: Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assays. Annexin V/PI double-staining was performed to assess cell apoptosis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. A xenograft mice model was used to assess the in vivo antitumor effects of corilagin alone or in combination with cisplatin.
Results: We for the first time showed that corilagin was effectively able to inhibit ESCC cell proliferation and induce cell apoptosis. Additionally, our results validated its antitumor effects in vivo using a xenograft mouse model. Mechanistically, we found that corilagin caused significant DNA damage in ESCC cells. We found that corilagin could significantly attenuate the expression of the E3 ubiquitin ligase RING finger protein 8 (RNF8) through ubiquitin-proteasome pathway, leading to the inability of DNA damage repair response and eventually causing cell apoptosis. Furthermore, we also showed that corilagin substantially enhanced the antitumor effects of chemotherapy drug cisplatin both in vitro and in vivo.
Conclusion: Our results not only provided novel and previously unrecognized evidences for corilagin-induced tumor suppression through inducing DNA damage and targeting RNF8 in ESCC, but also highlighted that corilagin might serve as an adjunctive treatment to conventional chemotherapeutic drugs in ESCC patients.
Corilagin, RNF8, DNA damage, esophageal squamous cell carcinoma, cisplatin, chemosensitivity.
Department of Infection Control, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130, Guangzhou University of Chinese Medicine, Guangzhou 510006, Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangzhou University of Chinese Medicine, Guangzhou 510006, Department of General Practice Center, Nanhai Hospital of Southern Medical University, Foshan 528244