Broad-Spectrum Cytotoxic Activity of 18β-Glycyrrhetinic Acid in Cervical Cancer Cells with Diverse Genetic Backgrounds

국문 초록 (Abstract)

감초 뿌리에서 유래한 트리테르페노이드인 18β-glycyrrhetinic acid(18β-GA)는 항산화, 항염, 항암효과 등이 밝혀져 왔으나, 다양한 암종에서의 항종양 효과와 작용 기전은 여전히 충분히 규명되지 않은 실정이다. 본 연구에서는 18β-GA의 세포독성을 평가하기 위해 AGS (위암), ASPC-1 (췌장암), HCT116, HT-29, LS174T (대장암), NCI-H460 (폐암) 및 여러 자궁경부암 세포주를 포함한 다양한 인간 암 세포주를 대상으로 항종양 효과를 스크리닝하였다. 본 연구에서 테스트 된 암세포주들 모두에서 농도 의존적으로 세포 생존률 감소가 관찰되었으며, 특히 HeLa 세포가 가장 높은 민감도를 보였다. 추가로 자궁경부암 세포주에서 18β-GA에 의한 항종양효과 기전이나 세포주 유전적 특성에 따른 차이는 거의 분석된 바가 없어, 인간유두종바이러스(Human papilloma virus, HPV) 감염유형과 유전적 배경이 상이한 네 가지 자궁경부암 세포주(HeLa, SiHa, CaSki, SNU-17)를 대상으로 항종양 효과에 대한 추가분석을 시행하였다. 18β-GA 처리 시 자궁경부암 세포주의 세포사멸 증가, 핵 형태 변형, 세포 주기 진행 변형 등이 확인되었으며, 이러한 효과의 민감도는 세포주에 따라 차이를 보였다. 종합적으로, 본 연구 결과는 18β-GA가 여러 암 유형에서 항종양 활성을 나타낼 수 있고 특히 유전적 배경이 다른 자궁경부암의 타입에 따라 보다 우세한 작용 기전이 존재할 수 있다는 가능성을 제시하며, 차등적 분자 기전과 치료적 가능성에 대한 추가 연구의 기초자료로 활용될 가치가 있다.

다국어 초록 (Multilingual Abstract)

18β-Glycyrrhetinic acid (18β-GA), a triterpenoid compound derived from licorice root, has been reported to possess antioxidant, anti-inflammatory, and anticancer properties; however, its antitumor effects across diverse cancer types and the underlying molecular mechanisms remain incompletely elucidated. In this study, the cytotoxic effects of 18β-GA were systematically evaluated in a panel of human cancer cell lines, including gastric cancer (AGS), pancreatic cancer (ASPC-1), colorectal cancer (HCT116, HT-29, and LS174T), lung cancer (NCI-H460), and multiple cervical cancer cell lines. Treatment with 18β-GA resulted in a concentration-dependent reduction in cell viability in all tested cancer cell lines, with HeLa cells exhibiting the highest sensitivity. Given the limited understanding of the antitumor mechanisms of 18β-GA in cervical cancer and the potential influence of genetic heterogeneity, further analyses were conducted using four cervical cancer cell lines with distinct human papillomavirus (HPV) status and genetic backgrounds (HeLa, SiHa, CaSki, and SNU-17). Exposure to 18β-GA significantly increased apoptosis, induced nuclear morphological abnormalities, and altered cell-cycle progression in cervical cancer cells, although the degree of sensitivity varied among the different cell lines. Collectively, these findings demonstrate that 18β-GA exerts broad-spectrum antitumor activity across multiple cancer types and suggest that its anticancer effects in cervical cancer may be modulated by HPV status and genetic background. This study provides a foundation for further investigation into the differential molecular mechanisms and therapeutic potential of 18β-GA in genetically diverse cervical cancer models.

목차 (Table of Contents)

• CONTENTS
• I. Introduction 1
• II. Materials and Methods 4
• 1. Cell culture 4
• 2. MTT assay 4
• 3. Apoptotic cell morphology 5
• 4. Cell cycle analysis 6
• 5. Apoptosis analysis by Annexin V/PI staining 6
• 6. Migration assay 7
• 7. RT-PCR analysis 8
• 8. Statistical analyses 9
• III. Results 10
• 1. 18β-glycyrrhetinic acid inhibits cell proliferation in cervical cancer cells as well as various human cancer cells 10
• 2. 18β-glycyrrhetinic acid causes nuclear changes in cervical cancer cells 14
• 3. Cervical cancer cell lines exhibit differential sensitivity to 18β-glycyrrhetinic acid-induced apoptosis 18
• 4. 18β-glycyrrhetinic acid inhibits migration of cervical cancer cells 22
• 5. 18β-glycyrrhetinic acid modulates cell cycle distribution in cervical cancer cells 26
• 6. 18β-glycyrrhetinic acid induces alterations in E6 and E7 mRNA expression in cervical cancer cells 29
• IV. Discussion 31
• V. Conclusion 39
• Ⅵ. References 40