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Non-aqueous extract of Citrus unshiu Markovich peel inhibits growth, migration, and stemness
in human cervical cancer cells
Ye Seul Choi and Hye Jin Jung
Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 336-708, Republic of Korea
BACKGROUND METHODS
Citrus unshiu Markovich peel has been used as a traditional medicine for the
treatment of various diseases in East Asia. Recently, the anticancer activities and
mechanisms of action of C. unshiu Markovich peel extracts have been reported in Cell growth, migration, and invasion inhibitory effects were confirmed to MTT
several cancer cells, but there has been no study on the therapeutic effect of this assay, colony formation assay, and invasion assay. Cell cycle arrest and
natural product on cervical cancer cells. apoptosis effects were analyzed by flow cytometry. The expression levels of
Cervical cancer is the second most commonly cancer and the fourth leading cause of molecular markers were obtained by Western blot analysis. DNA
cancer death in women. Late-stage cervical cancers are popularly considered fragmentation and ROS activity by CECU in HeLa cells were tested using
incurable, and treatment strategy are very limited. Therefore, it is necessary to DAPI staining and DCFH-DA staining.
research and develop cervical cancer anticancer drug or treatment strategies.
HeLa–derived cancer stem-like cell growth and sphere forming inhibitory
AIM results were obtained by luminescence assay and tumorsphere-forming assay.
The present study aimed to evaluate the anticancer effect of chloroform extract of The size and number of spheres were counted using microscope. The activity
Citrus unshiu Markovich peel (CECU) in human cervical cancer cell line HeLa cells of cancer stemness regulators was confirmed by Western blot analysis.
and HeLa derived cancer stem-like cells.
RESULTS
Figure 1. Figure 2.
A
A
B
CECU effectively suppresses
the viability of HeLa CSCs.
B
CECU inhibits the colony forming ability of HeLa cells.
CECU dose-dependently inhibits the cell growth of HeLa cells.
C
D
CECU inhibits the number and
size of tumorspheres in HeLa
CSCs.
CECU significantly inhibits the invasion of HeLa cells. C
E CECU inhibits the migration of HeLa cells.
CECU induces G2/M phase cell CECU inhibits the
cycle arrest in HeLa cells. expression levels of key
stemness markers in HeLa
CSCs.
G
REFERENCES
F
• Ahn KI, Choi EO, Kwon DH, HwangBo H, Kim MY,
Kim HJ, Ji SY, Hong SH, Jeong JW, Park C, et al.
Induction of apoptosis by ethanol extract of Citrus
CECU inactivates ERK/AKT pathway and unshiu Markovich peel in human bladder cancer T24
CECU induces apoptosis in HeLa cells. upregulates p53 and p21. CECU also activates cells through ROS-mediated inactivation of the
extrinsic and intrinsic apoptosis pathways. PI3K/Akt pathway. Biosci Trends. 2017; 11: 565-573.
H doi: 10.5582/bst.2017.01218
I • He C, Mao D, Hua G, et al. The Hippo/YAP pathway
interacts with EGFR signaling and HPV oncoproteins
to regulate cervical cancer progression. EMBO Mol
Med. 2015;7(11):1426-1449.
doi:10.15252/emmm.201404976
• Wang M, Xue Y, Shen L, et al. Inhibition of SGK1
confers vulnerability to redox dysregulation in cervical
CECU induces DNA fragmentation of HeLa cells. cancer. Redox Biol. 2019;24:101225.
CECU dose not affect ROS expression. doi:10.1016/j.redox.2019.101225
CONCLUSION
• CECU significantly inhibits the growth, colony formation, and invasion of HeLa cells via induction of G2/M phase cell cycle arrest and
apoptosis in a ROS-independent manner.
• CECU also suppresses the growth and sphere formation of HeLa cancer stem-like cells (CSCs).
• Therefore, our results demonstrate the anticancer potential of Citrus unshiu Markovich peel for the prevention and treatment of cervical cancer.
Contact information
.Ye Seul Choi
Sun Moon University
Email: yesll96@naver.com
