Kochia scoparia induces apoptosis of oral cancer cells in vitro and in heterotopic tumors.
BACKGROUND
Kochia scoparia grows commonly in China, Japan, and Korea and its mature fruit has been used throughout the area in traditional medicine to treat diseases including skin problems and inflammatory and allergic disease. More importantly, Kochia scoparia has been prescribed to treat the malignant tumor of head and neck region and breast mass. Although it has been proposed as an anti-cancer agent for several cancers, its exact in vivo anti-cancer properties and the molecular mechanisms underlying its effects are poorly understood.


OBJECTIVE
To evaluate the anti-cancer activity of the methanol extract of K. scoparia, mature fruit (MEKS) on oral squamous cell carcinoma (OSCC) and to explore its mode of action.


METHODS
To assess proliferation inhibition and apoptosis induction by MEKS, MTT assays, cell analysis, ANNEXIN V and PI double staining, and Hoechst 33342 staining were performed. The activation of caspases and the MAP kinase p38 was evaluated using Western blot analysis. The anti-cancer properties of MEKS in vivo were elucidated in a heterotopic OSCC animal model.


RESULTS
After OSCC cells were treated with MEKS, the numbers of sub-G1 accumulated cells and apoptotic bodies increased, indicating that MEKS inhibited OSCC cell proliferation selectively through induction of apoptosis. Apoptosis of MEKS-treated OSCC cells was induced in a dose-dependent manner by caspase-3 and -9 activation. In addition, pretreatment with p38 inhibitor SB203580 in combination with MEKS significantly prevented MEKS-induced apoptosis in OSCC cells and also decreased cleaved capase 3, 9, and cleaved PARP activity in western blotting. MEKS treatment significantly increased the apoptosis of OSCC and inhibited tumour growth in our animal model.


CONCLUSIONS
Taken together, these results indicated that MEKS induced apoptosis of OSCC cells through caspase activation involving the p38 MAPK pathway. MEKS could be a promising anti-cancer candidate for OSCC treatment.
Department of Oral Pathology, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Hye-Yeon
HY
Han
Department of Oral Pathology, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Haeng-Eun
HE
Lee
Department of Oral Physiology, BK21 Plus Project, School of Dentistry, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Hyung Joon
HJ
Kim
Department of Preventive and Community Dentistry, BK21 Plus project, School of Dentistry, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Seung-Hwa
SH
Jeong
Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Jung-Hoon
JH
Kim
Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, South Korea.
Hyungwoo
H
Kim
Department of Oral Pathology, BK21 Plus project, School of Dentistry, Pusan National University, Yangsan, Gyeongnam 50612, South Korea. Electronic address: apollon@pusan.ac.kr.
Mi Heon
MH
Ryu
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027467:Bassia scoparia / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005638:Fruit / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D000432:Methanol / Q000737:chemistry; D008809:Mice, Inbred C3H; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry; D000077195:Squamous Cell Carcinoma of Head and Neck; D047368:Tumor Burden / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012997:Solvents; D011065:Poly(ADP-ribose) Polymerases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D017239:Paclitaxel; D000432:Methanol
Anti-cancer property; In vivo models; Kochia scoparia; Oral cancer; Traditional Chinese medicine; p38