Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway

Hantae Jo,Jeong-Hyun Oh,Dong-Wook Park,Changho Lee,Churl K. Min 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (△ψm), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of △ψm, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetateeinduced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway

Jo, Hantae,Oh, Jeong-Hyun,Park, Dong-Wook,Lee, Changho,Min, Churl K. The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.1

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

Ginsenoside 20(S)-protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis

Hantae Jo,Dongmin Jang,Sun Kyu Park,Mi-Gi Lee,Byungsun Cha,Chaewon Park,Yong Sub Shin,Hyein Park,Jin-myoung Baek,Hyojin Heo,Sofia Brito,Hyun Gyu Hwan,Sehyun Chae,Shao-wei Yan,Changho Lee,Churl K. Min 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.1

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

Endometrial cancer invasion depends on cancer‐derived tumor necrosis factor‐α and stromal derived hepatocyte growth factor

Choi, Dong Soon,Kim, Hyun‐,Jin,Yoon, Jong‐,Hyuck,Yoo, Seung‐,Chul,Jo, Hantae,Lee, So Yeon,Min, Churl K.,Ryu, Hee‐,Sug Wiley Subscription Services, Inc., A Wiley Company 2009 International journal of cancer: Journal internati Vol.124 No.11

<P><B>Abstract</B></P><P>Cancer invasion is an outcome of interactions of the cancer and the host cell. It is now becoming increasingly clear that ovarian hormones have a huge influence on such intercommunications in various types of cancers. Estrogen is known to aggravate the aggressiveness of the endometrial cancer whereas progesterone seems to act as a negative factor. Insight into the mode of ovarian hormonal actions could come from the studies of its regulation of the paracrine interactions between the endometrial cancer and the normal stromal cells during the cancer invasion. In this context, we report here that estrogen promotes the endometrial cancer invasion by inducing humoral interactions between the cancer and the stromal cells, <I>i.e</I>., estrogen stimulates tumor necrosis factor‐α expression from the endometrial cancer cells, which, in turn, induces the stromal expression of hepatocyte growth factor (HGF), conferring the enhanced NK4 (HGF‐antagonist/angiogenesis inhibitor)‐sensitive invasion characteristic of the endometrial cancer cells. Additionally, we demonstrate a close correlation of the invasion of endometrial cancer cells with the expression and dimerization of integrin α<SUB>v</SUB>β<SUB>5</SUB> as well as the activation of focal adhesion kinase as the consequences of paracrine interactions. Thus, understanding of paracrine interactions of cancer cells with host stromal cells can yield new insight into the architecture and function of cancer invasion and metastasis, leading to a development of a new cancer therapeutic intervention. © 2008 Wiley‐Liss, Inc.</P>

파우더와 오일의 배합 비율이 탈크 프리 프레스드 파우더 제형의 안정성에 미치는 영향에 관한 연구

오지원 ( Ji Won Oh ),김현지 ( Hyun Jee Kim ),곽병문 ( Byeong Mun Kwak ),조한태 ( Hantae Jo ),이미기 ( Mi-gi Lee ),빈범호 ( Bum-ho Bin ) 대한화장품학회 2021 대한화장품학회지 Vol.47 No.1

프레스드 파우더의 주요 안정성 요인으로 경도와 낙하 안정도가 있다. 일반적으로 탈크가 포함된 프레스드 파우더의 경우 경도와 낙하 안정도를 고르게 충족시키며 사용감도 우수하지만 최근 탈크의 석면 이슈로 인해 대체를 원하는 고객들이 늘고 있다. 따라서 안정성을 유지하면서 사용감도 떨어지지 않는 탈크 프리 프레스드파우더 제형의 개발이 시급하다. 본 연구에서는 탈크 프리 프레스드 파우더를 만들기 위한 최적의 원료 배합비율을 찾기 위한 실험을 진행하였다. 파우더에 주로 사용되는 원료들의 특성을 확인하고 비율을 변화시켜 실험하여 명도와 경도를 측정하고 낙하 시험을 실시하였다. 천연 마이카 함량이 합성 마이카보다 많거나, 코팅된 실리카 대신 논 코팅 실리카를 사용할 경우 탈크가 포함된 내용물보다 경도와 낙하 안정도는 낮지만 명도는 유사하였다. 반대로 합성 마이카 함량이 천연 마이카 함량과 동일하거나 높을 경우, 코팅된 실리카 함량이 논코팅 실리카 함량과 동일하거나 높은 경우에 탈크가 포함된 내용물의 경도, 낙하 안정도와는 유사하였으나 명도는 낮게 측정되었다. 탈크가 포함된 내용물보다 경도는 높지만 낙하 안정성은 떨어지는 현상도 발견하여 경도와 낙하 안정성의 상관관계에 대해서는 추가적인 연구가 필요할 것으로 생각된다. The main stability factors of the pressed powder include hardness and drop stability. In general, for pressed powder with talc, the hardness and drop stability are evenly met and the skin texture is excellent. Recently, more than ever customers are looking for a replacement due to asbestos issue of talc. Therefore, it is urgent to develop a pressed powder formulation without talc that maintains stability and does not lose its sense of use. In this study, experiments were conducted to find the optimal ingredients mixing ratio to make talc-free pressed powder. The characteristics of raw materials used mainly in powder were checked and the ratio was changed, and the lightness and hardness were measured and drop test was conducted. If the natural mica ratio was higher than the synthetic mica or non-coated silica was used instead of the coated silica, the hardness and drop stability were lower than the content containing talc, but the lightness was similar. Conversely, if the synthetic mica ratio was equal to or higher than the natural mica ratio and the coated silica ratio was equal to or higher than the non-coated silica ratio, the hardness and drop stability of the content containing talc were similar, but the lightness was low. It was found that the hardness was higher than the content containing talc, but the drop stability was lower. Therefore, further study of the correlation between hardness and fall stability is also thought to be necessary.