The anticancer mechanism of 2'-hydroxycinnamaldehyde in human head and neck cancer cells.
Cinnamaldehyde has been shown to effectively induce apoptosis in a number of human cancer cells. In the present study, cinnamaldehyde derivative-induced apoptosis and its signaling pathways were assessed in p53-wild (SGT) and p53-mutant (YD-10B) human head and neck cancer cells. The cinnamaldehyde derivatives, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoyloxycinnamaldehyde (BCA), exhibited powerful anti-proliferative effects on SGT and YD-10B cells. The apoptotic effect induced by HCA or BCA was supported by caspase-3, -7, -9 and PARP activation, and confirmed by Annexin V-FITC/PI double staining. HCA induced the expression of p21 in both SGT and YD-10B cells. Furthermore, HCA induced the level of pro-apoptotic Bak1 expression while decreasing the level of anti-apoptotic Bcl-2 in both cell lines, suggesting that HCA induced the cell death pathway in a p53-independent manner. HCA also induced the expression of LC3B in SGT and YD-10B cells. Following pre-incubation with the autophagy inhibitor 3-MA, HCA-induced apoptosis was largely increased in SGT cells, while inhibited in YD-10B cells, suggesting that autophagy may actively contribute to HCA-induced apoptosis. Taken together, these observations suggest that HCA may be an effective therapeutic agent in the treatment of head and neck cancer regardless of p53 status.
Department of Pathology, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
Sang-Gun
SG
Ahn
Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
Young-Hee
YH
Jin
Department of Oral and Maxillofacial Pathology, College of Dentistry, Daejeon Dental Hospital, Wonkwang Bone Regeneration Research Institute, Wonkwang University, Daejeon 302-120, Republic of Korea.
Jung-Hoon
JH
Yoon
Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
Soo-A
SA
Kim
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002934:Cinnamates / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D017304:Annexin A5; D002934:Cinnamates; D017382:Reactive Oxygen Species; C117045:p-hydroxycinnamaldehyde