Chae Ryun Lee

Publications (4)14.68 Total impact

• Article: Cyclosporin A suppresses prostate cancer cell growth through CaMKKβ/AMPK-mediated inhibition of mTORC1 signaling.

  Chae Ryun Lee, Jung Nyeo Chun, Sang-Yeob Kim, Soonbum Park, Su-Hwa Kim, Eun-Jung Park, In-San Kim, Nam-Hyuk Cho, In-Gyu Kim, Insuk So, Tae Woo Kim, Ju-Hong Jeon
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  ABSTRACT: Cyclosporin A (CsA) has antitumor effects on various cancers including prostate cancer. However, its antitumor mechanism is poorly understood. In this study, we showed that AMP-activated protein kinase (AMPK) mediates the antitumor effect of CsA on prostate cancer cells. CsA attenuated cell growth by inducing a G1 arrest through the inhibition of mTOR complex 1 (mTORC1) signaling. In this context, Akt was paradoxically activated downstream of the EGF receptor (EGFR)-mediated increase in phosphatidylinositol 3,4,5-trisphosphate (PIP₃) production. However, CsA also caused a Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ)-dependent activation of AMPK, which inhibits mTORC1 signaling; this led to ineffective Akt signaling. An EGFR or Akt inhibitor increased the growth suppressive activity of CsA, whereas the combination of an AMPK inhibitor and CsA markedly rescued cells from the G1 arrest and increased cell growth. These results provide novel insights into the molecular mechanisms of CsA on cancer signaling pathways.
  Biochemical pharmacology 05/2012; 84(4):425-31. · 4.25 Impact Factor
• Article: Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells.

  Su-Hwa Kim, Eun-Jung Park, Chae Ryun Lee, Jung Nyeo Chun, Nam-Hyuk Cho, In-Gyu Kim, Sanghoon Lee, Tae Woo Kim, Hyun Ho Park, Insuk So, Ju-Hong Jeon
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  ABSTRACT: Geraniol, an acyclic dietary monoterpene, suppresses prostate cancer growth and enhances docetaxel chemosensitivity in cultured cell or xenograft tumor models. However, the mechanisms of the geraniol action against prostate cancer are largely unknown. In this study, we investigated the cellular and molecular mechanisms of geraniol-induced cell death in PC-3 prostate cancer cells. Among the examined structurally and functionally similar monoterpenes, geraniol potently induced apoptosis and autophagy. Although independent processes, apoptosis and autophagy acted as cooperative partners to elicit geraniol-induced cell death in PC-3 cells. At a molecular level, geraniol inhibited AKT signaling and activated AMPK signaling, resulting in mTOR inhibition. Combined treatment of AKT inhibitor and AMPK activator markedly suppressed cell growth compared to either treatment alone. Our findings provide insight into future investigations that are aimed at elucidating the role of apoptosis and autophagy in prostate cancer therapy and at developing anticancer strategies co-targeting AKT and AMPK.
  International Journal of Oncology 12/2011; 40(5):1683-90. · 2.40 Impact Factor
• Article: SK&F 96365 induces apoptosis and autophagy by inhibiting Akt–mTOR signaling in A7r5 cells

  Eun-Jung Park, Sang-Yeob Kim, Su-Hwa Kim, Chae Ryun Lee, In-San Kim, Jong Kwan Park, Sung Won Lee, Byung Joo Kim, Jung Nyeo Chun, Insuk So, Ju-Hong Jeon
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  ABSTRACT: SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt–mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.Highlights► SK&F 96365 induces apoptosis and autophagy. ► Combined suppression of SK&F 96365-induced apoptosis and autophagy provokes necrosis. ► SK&F 96365 inhibits Akt–mTOR signaling pathways.
  Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 07/2011; 1813(12):2157-2164. · 5.54 Impact Factor
• Article: Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways.

  Su-Hwa Kim, Hyun Cheol Bae, Eun-Jung Park, Chae Ryun Lee, Byung-Joo Kim, Sanghoon Lee, Hyun Ho Park, Sung-Joon Kim, Insuk So, Tae Woo Kim, Ju-Hong Jeon
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  ABSTRACT: The progression of prostate cancer is associated with escape from cell cycle arrest and apoptosis under androgen-depleted conditions. Here, we found that geraniol, a naturally occurring monoterpene, induces cell cycle arrest and apoptosis in cultured cells and tumor grafted mice using PC-3 prostate cancer cells. Geraniol modulated the expression of various cell cycle regulators and Bcl-2 family proteins in PC-3 cells in vitro and in vivo. Furthermore, we showed that the combination of sub-optimal doses of geraniol and docetaxel noticeably suppresses prostate cancer growth in cultured cells and tumor xenograft mice. Therefore, our findings provide insight into unraveling the mechanisms underlying escape from cell cycle arrest and apoptosis and developing therapeutic strategies against prostate cancer.
  Biochemical and Biophysical Research Communications 02/2011; 407(1):129-34. · 2.48 Impact Factor