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Ginsenoside 20(S)-Protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis
- Alternative Title
- Ginsenoside 20(S)-Protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis
- Author(s)
- 박선규
- Alternative Author(s)
- Sun Kyu Park
- Advisor
- 민철기
- Department
- 일반대학원 생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2018-02
- Language
- eng
- Abstract
- 주요한 ginsenoside 대사물질인 20(S)-protopanaxadiol은 여러 암 세포에서 성장과 증식을 억제하는 것으로 나타났다. 이 연구는 인간 자궁 내막 암에 대한 항암 활성을 평가하려는 시도로 시작되었다. 인간 자궁 내막 암 HEC-1A 세포를 각각 다른 농도의 20(S)-PPD로 배양하고 세포 독성은 MTT assay로 평가되었다. 세포사멸의 발생은 Annexin V-FITC/PI 이중 염색과 세포주기 분석에 의해 검출되었다. Cleaved PARP와 caspase-9 발현은 Western blotting 분석에 의해 밝혀졌다. 20(S)-PPD는 농도 의존적으로 HEC-1A 세포의 증식을 24시간 동안 3.5 μM의 IC50값으로 억제하였다. 20(S)-PPD로 처리한 후 HEC-1A 세포는 PI로 염색된 세포에서 형태학적 분석에 의해 관찰된 바와 같이 전형적인 세포사멸을 나타냈다. Annexin V-FITC 양성 세포의 백분율은 0, 2.5 및 5 μM의 20(S)-PPD로 처리한 HEC-1A 세포에서 각각 0%, 10.8% 및 58.1%였다. HEC-1A 세포를 BALB/c 암컷 누드 마우스의 좌측면에 접종하여 생체 외 이종 이식 자궁 내막 종양 모델을 제조하였다. 20(S)-PPD를 10, 40 및 80 mg/kg의 용량으로 1주일에 3회 피하 주사하고, 80 mg/kg의 투여 양에서 종양 성장 억제율을 18%까지 이르게 하였다. 이러한 사건은 암조직에서 caspase-9 과 PARP 절단의 활성화를 수반하였다. 결론적으로, 20(S)-PPD는 세포 증식을 억제하여 caspase 매개 세포사멸 경로에 의해 자궁내막암 세포의 사멸을 유도한다.
- Alternative Abstract
- 20(S)-Protopanaxadiol (PPD), a major ginsenoside metabolite, has been shown to inhibit the growth and proliferation of several cancer cells. This study was initiated with an attempt to evaluate its anticancer activity toward human endometrial cancer. Human endometrial cancer (HEC)-1A cells were incubated with different concentrations of 20(S)-PPD and its cytotoxicity was evaluated by the MTT assay. Occurrence of apoptosis was detected by annexin V-FITC/PI double staining and by cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and caspase-9 appearances were determined by Western blotting analysis. 20(S)-PPD dose-dependently inhibited cell proliferation of HEC-1A cells with an IC50 value of 3.5 μM at 24 hrs. HEC-1A cells treated with 20(S)-PPD exhibited typical apoptosis as observed by morphological analysis in cells, which bore close resemblance to taxol treatment. The percentages of annexin V-FITC positive cells were 0%, 10.8% and 58.1% in HEC-1A cells treated with 0, 2.5 and 5 μM of 20(S)-PPD, respectively, for 24 hrs. HEC-1A cells then were inoculated into the left flank of BALB/c female nude mice to produce an in vivo xenograft endometrial tumor model. 20(S)-PPD was subcutaneously injected three times a week for 3 weeks at the doses of 10, 40, and 80 mg/kg, and its tumor growth inhibition rate reached as high as 18% at the dose of 80 mg/kg. These events paralleled the activation of caspase-9 and PARP cleavage. In conclusion, 20(S)-PPD is able to inhibit human endometrial cancer cell proliferation by inducing cancer cell death in a caspase-mediated apoptosis pathway.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Bioscience > 3. Theses(Master)
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