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[I. Chemical biology and drug discovery-15]



              Non-aqueous extract of Citrus unshiu Markovich peel inhibits


             growth, migration, and stemness in human cervical cancer cells




                                              Ye Seul Choi¹, Hye Jin Jung¹˙*

          ¹Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, Asan 336-708, Republic of

                                                          Korea




        Citrus unshiu Markovich peel has been used as a traditional medicine in China and Korea by exhibiting antioxidant,
        anti-allergic, anti-inflammatory, and anticancer activities. In previous reports, the bioactivities of the natural product

        have been mainly identified from water or ethanol extract at concentrations of 200-1500 µg/mL. The present study

        aimed  to  investigate the anticancer  activity and molecular  mechanism  of  the  chloroform  extract  of  C.  unshiu
        Markovich peel (CECU) in HeLa human cervical carcinoma cells. The results showed that CECU effectively inhibited
        the growth and migration of HeLa cells at concentrations of 10-80 µg/mL. CECU led to cell cycle arrest at the G2/M

        phase and activation of extrinsic and intrinsic apoptosis pathways. Moreover, the growth inhibitory effect of CECU
        was involved in the inactivation of AKT and ERK signaling and the upregulation of p53 and p21, but not reactive

        oxygen species (ROS) generation. Furthermore,  CECU inhibited  the  stem-like  features  of  HeLa  cells  by
        downregulating key cancer stemness biomarkers. Therefore, the non-aqueous extract of C. unshiu Markovich peel

        may be an effective complementary and alternative medicine for the prevention and treatment of cervical cancer.
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