Apoptotic Response of Human Oral Squamous Carcinoma Cells to Etoposide

Etoposide에 대한 사람구강편평상피암종세포의 세포자멸사 반응

  • Kim, Gyoo-Cheon (Dept. of Oral Anatomy, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Lee, Kyoung-Duk (Dept. of Oral Anatomy, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Park, Jae-Hyun (Dept. of Oral Anatomy, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Kim, Duk-Han (Dept. of Oral Anatomy, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Park, Jeong-Kil (Dept. of Oral Conserve dentistry, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Park, June-Sang (Dept. of Oral Medicine, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University) ;
  • Park, Bong-Soo (Dept. of Oral Anatomy, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University)
  • 김규천 (부산대학교 치과대학 및 구강생물공학연구소 구강해부학교실) ;
  • 이경덕 (부산대학교 치과대학 및 구강생물공학연구소 구강해부학교실) ;
  • 박재현 (부산대학교 치과대학 및 구강생물공학연구소 구강해부학교실) ;
  • 김덕한 (부산대학교 치과대학 및 구강생물공학연구소 구강해부학교실) ;
  • 박정길 (부산대학교 치과대학 및 구강생물공학연구소 구강보존과학교실) ;
  • 박준상 (부산대학교 치과대학 및 구강생물공학연구소 구강내과학교실) ;
  • 박봉수 (부산대학교 치과대학 및 구강생물공학연구소 구강해부학교실)
  • Published : 2005.06.30


Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.

항암제의 연구는 화학물질에 민감한 암세포를 죽음에 이르게 하는 세포자멸사와 같은 다양한 세포기능에 초점을 맞추어 왔다. 그러나 약물이 유도한 세포의 죽음에 있어서 핵심적인 분자적 기작은 아직 잘 이해되지 않고 있다. Etoposide는 폐암과 고환암에 사용되는 항암제로서, 본 연구는 etoposide가 사람구강편평상피암종세포(OSC9)에도 세포독성효과와 세포자멸사를 일으키는지를 알아보기 위해 실행하였다. 이 실험에서 etoposide는 농도와 시간 의존적으로 OSC9 세포의 생존율를 현저하게 저해시켰다. TUNEL 염색과 Hoechst 염색을 이용한 핵의 형태학적 관찰에서는 etoposide에 의해 핵이 응축되고 분절되었다. p53의 발현은 48 시간에 증가했으며, etoposide 처리로 인해 caspase-3의 활성을 관찰할 수 있었으며, 그 기질에 해당되는 PARP 단백질은 116-kDa과 89-kDa으로 분절되었다. 위의 결과들은 OSC9 세포에서 etoposide가 유도한 세포자멸사는 caspase-3의 활성과 관련됨을 설명하고 있다.



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