Anticancer effects of Ixeris dentata (Thunb. ex Thunb.) nakai extract on human melanoma cells A375P and A375SM.
BACKGROUND
The plant species Taraxacum coreanum (TC), Youngia sonchifolia (YS), and Ixeris dentata (ID) belong to the family Compositae and are used for medicinal purposes in traditional medicine. However, the anticancer effects of TC, YS, and ID extracts and the underlying molecular mechanisms in melanoma cells have not been elucidated.


OBJECTIVE
To investigate the potential anticancer effects of TC, YS, and ID extracts on human melanoma cells and explore the potential pharmacological mechanisms in vitro and in vivo.


METHODS
In this comparative study, we investigated the effects of TC, YS, and ID extracts on cell proliferation in human melanoma A375P and A375SM cells using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Apoptotic cells were detected by 4',6-diamidino-2-phenylinodole (DAPI) staining. We also investigated whether the growth-inhibitory effects were associated with the induction of apoptosis and whether the mechanisms of cell death were the result of signaling molecules such as p53, Bax, Bcl-2, caspase-9, Poly-ADP ribose polymerase (PARP), and Erk (Extracellular signal-regulated protein kinase) 1/2. The in vivo antitumor effects were evaluated by measuring the tumor volume and weight and performing Terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay and immunohistochemistry (IHC) in tumor xenograft models.


RESULTS
TC, YS, and ID extracts effectively inhibited the growth of A375P and A375SM cells. In addition, several apoptotic events were observed following treatment, including DNA fragmentation and chromatin condensation by DAPI staining. The extracts increased p53, Bax, cleaved-caspase-9 and cleaved-PARP expression, whereas the expression of Bcl-2 was decreased in both cell lines. Furthermore, ID extract significantly inhibited the activation of Erk1/2 in both cell lines. Among the three extracts, ID had the strongest apoptotic effects. The administration of ID extract to mice inhibited tumor growth without any toxicity following 4 weeks of treatment. This extract increased the expression of apoptotic cells and p53 protein and decreased phospho-Erk1/2 protein.


CONCLUSIONS
TC, YS, and ID extracts suppress the growth of human melanoma cells through apoptosis. Among these extracts, ID has the strongest anticancer and apoptotic effects. It induces apoptosis through the inhibition of Erk1/2 in A375P and A375SM human melanoma cells and in tumor xenograft models and may be a potential chemotherapeutic agent against melanoma.
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Hae Nim
HN
Lee
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Seong Ah
SA
Shin
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Gang Sik
GS
Choo
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Hyeong Jin
HJ
Kim
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Young Seok
YS
Park
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Byung Kwon
BK
Park
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Byeong Soo
BS
Kim
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea.
Sang Ki
SK
Kim
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, South Korea.
Sung Dae
SD
Cho
Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 500-712, South Korea.
Jeong Seok
JS
Nam
School of Food Science and Technology, Chung-ang University, Ansung 456-756, South Korea.
Chang Sun
CS
Choi
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, South Korea. Electronic address: wangza@kongju.ac.kr.
Ji Youn
JY
Jung
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019659:Asteraceae / Q000737:chemistry*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D031205:Taraxacum / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D053453:Caspase 9
A375P; A375SM; Anticancer; Ixeris dentata; Melanoma