http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Biphasic Activity of Chloroquine in Human Colorectal Cancer Cells
박덕배,이영기 한국발생생물학회 2014 발생과 생식 Vol.18 No.4
Autophagy is a homeostatic degradation process that is involved in tumor development and normaldevelopment. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagyresults in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and iscurrently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of thesedual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in doseandtime-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability atlow concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses ofCQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with highdoses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor orLMP inducer, in concentration-dependent manner.
박덕배,김창미,천민석,유경자,Park, Deok-Bae,Kim, Chang-Mee,Cheon, Min-Seok,Ryu, Kyung-Za The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.3
We examined the effects of EGTA and verapamil on phorbol ester-and forskolin-stimulated LH releases and $LH{\beta}$ subunit mRNA levels in order to verify the role of extracellular $Ca^{++}$ on PKC- or cAMP-induced increases in LH release and $LH{\beta}$ subunit mRNA levels in cultured anterior pituitary cells of rat. Forskolin-stimulated $LH{\beta}$ subunit mRNA levels as well as LH release were all suppressed by prevention of $Ca^{++}$ mobilization from extracellular environment, after the treatment of EGTA as a $Ca^{++}$ chelator or verapamil as a $Ca^{++}$ channel blocker. PMA-stimulated $LH{\beta}$ subunit mRNA levels were also suppressed by the treatment of EGTA and verapamil, while PMA-induced LH release was not affected. From the present study, it is, therefore, suggested that PKC activation and cAMP elevation all stimulate $LH{\beta}$ subunit mRNA levels and these are extracellular $Ca^{++}$-dependent. However, LH releases by PKC activation and cAMP increase seem to be different each other. LH release by PKC activation is thought to be independent of extracellular $Ca^{++}$. On the other hand, cAMP stimulated-LH release is thought to be dependent on the entry of extracellular $Ca^{++}$. 흰쥐 뇌하수체 전엽배양세포에서 PKC나 cAMP에 의한 LH 분비와 $LH{\beta}$subunit mRNA 증가과정에서 세포외 $Ca^{++}$의 역할을 검증하기 위하여 phorbol ester와 forskolin에 의해 촉진된 LH 분비와 $LH{\beta}$ subunit mRNA 수준에 미치는 EGTA와 verapamil의 영향을 조사하였다. Forskolin에 의해 촉진된 LH 분비와 $LH{\beta}$ subunit mRNA 수준은 $Ca^{++}$ chelator인 EGTA나 $Ca^{++}$ 채널차단제인 verapamil의 처리로 세포외부로부터 $Ca^{++}$의 이동을 억제시켰을때 모두 감소하였다. PMA에 의해 유도된 LH 분비는 EGTA와 verapamil 처리에 의해 영향을 받지 않았으나 PMA에 의해 촉진된 $LH{\beta}$ subunit mRNA는 억제되었다. 따라서 본 연구에 의하면 PKC 활성화나 세포내 cAMP 농도 증가는 $LH{\beta}$ subunit mRNA 수준을 증가시키며 이러한 과정은 세포외 $Ca^{++}$ 의존적인 것으로 생각된다. 그러나 PKC 활성화나 cAMP 증가에 의한 세포외 $Ca^{++}$의 역할이 서로 다른 양상을 보인다. PKC 활성화에 의한 LH 분비는 세포외 $Ca^{++}$에 비의존적이나 cAMP에 의해 촉진된 LH 분비는 세포외 $Ca^{++}$ 유입의 영향을 받는 것으로 사료된다.
흰쥐뇌하수체 배양세포에서 FSH 유전자 발현 및 FSH 분비 조절
박덕배,유경자,박용빈,감경윤,천민석 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.2
Background : FSH is a heterodimeric glycoprotein and is composed of αand β subunits. αsubunit is common to FSH and LH, while an unique β subunit determines the biological specificity of each hormone. The synthesis of β subunit is the primary rate-limiting step in the synthesis of each hormone. Although FSH plays a pivotal role in folliculogenesis and ovulation, very little studies have been performed on the regulation of FSH β gene expression. Therefore, the present study attempted to examine the effect of GnRH or activin on the expression of FSH β mRNA as well as FSH release and signaling pathway involved in their actions. Methods : The primary cultures of rat anterior pituitary were used for this study. To determine FSH β mRNA levels, northern blotting method was used. The concentration of FSH in the culture medium was evaluated by using a specific radioimmunoassay for rat FSH. Results : PMA, an activator of PKC, increased FSH β mRNA levels and FSH release, whereas forskolin, an activator of adenlase, showed no effect. The application of GnRH augmented FSH release, but not FSH β mRNA levels. However, the administration of activin increased FSH β mRNA levels as well as FSH release. Staurosporine, an inhibitor of PKC, suppressed activin-induced increment of FSH β mRNA levels and FSH release. Conclusion : The present study demonstrated that activin rather than GnRH is a major regulator for FSH β mRNA expression, and suggest that PKC-dependent pathway is also involved in the action of activin on the expression of FSH β mRNA and FSH release(J Kor Soc Endocrinol 15:179-189, 2000).