In vitro and in vivo anti-cancer activity of silymarin on oral cancer
Dong-Hoon Won,
Lee-Han Kim,
Boonsil Jang,
In-Hyoung Yang,
Hye-Jeong Kwon,
Bohwan Jin,
Seung Hyun Oh,
Ju-Hee Kang,
Seong-Doo Hong,
Ji-Ae Shin,
Sung-Dae Cho
Affiliations
Dong-Hoon Won
Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
Lee-Han Kim
Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea
Boonsil Jang
Department of Dental Hygiene, Sorabol College, Gyeongju-si, Republic of Korea
In-Hyoung Yang
Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea
Hye-Jeong Kwon
Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
Bohwan Jin
Laboratory Animal Center, CHA University and CHA Bio Complex, Seongnam, Republic of Korea
Seung Hyun Oh
National Cancer Center, Goyang-si, Republic of Korea
Ju-Hee Kang
National Cancer Center, Goyang-si, Republic of Korea
Seong-Doo Hong
Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
Ji-Ae Shin
Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
Sung-Dae Cho
Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
Silymarin, a standardized extract from milk thistle fruits has been found to exhibit anti-cancer effects against various cancers. Here, we explored the anti-cancer activity of silymarin and its molecular target in human oral cancer in vitro and in vivo. Silymarin dose-dependently inhibited the proliferation of HSC-4 oral cancer cells and promoted caspase-dependent apoptosis. A human apoptosis protein array kit showed that death receptor 5 may be involved in silymarin-induced apoptosis, which was also shown through western blotting, immunocytochemistry, and reverse transcription-polymerase chain reaction. Silymarin increased cleaved caspase-8 and truncated Bid, leading to accumulation of cytochrome c. In addition, silymarin activated death receptor 5/caspase-8 to induce apoptotic cell death in two other oral cancer cell lines (YD15 and Ca9.22). Silymarin also suppressed tumor growth and volume without any hepatic or renal toxicity in vivo. Taken together, these results provide in vitro and in vivo evidence supporting the anti-cancer effect of silymarin and death receptor 5, and caspase-8 may be essential players in silymarin-mediated apoptosis in oral cancer.
