摘要:
Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the antitumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells. Interestingly, the inhibitory effect of melatonin on proliferation in SH-SY5Y cells is more potent than that in U118 cells. In contrast, this inhibitory effect on the normal cells is absent. The antitumor effects of melatonin are positively associated with its metabolite N-acetylserotonin (NAS). Unexpectedly, CYP1B1 is, for first time, identified to localize in the mitochondria of tumor cells, and it metabolizes melatonin to form NAS in situ, which subsequently triggers mitochondria-dependent apoptosis in cancer cells. In normal cells, NAS does not induce apoptosis. A remarkable individual variation on CYP1B1 expression was also detected in human tumor tissue. These findings provide the novel mechanisms regarding the antitumor effects of melatonin in the level of mitochondria. Thus, we hypothesize that CYP1B1 overexpression in mitochondria would significantly enhance the antitumor effects of melatonin. Mitochondrial CYP1B1 can potentially serve as a specific target to modify the therapeutic and biological effects of melatonin on cancer patients.
作者机构:
[王超; 谭成富; 刘薇薇; 杜琳; 宋瑾; 严洁; 唐雅妮; 冯果; 陈美琳; 阳晶晶; 李姣兰] College of Acu-moxibustion and Massage, Hunan University of Traditional Chinese Medicine, Changsha 410007, China
作者:
Liu Mi;Liu Yi;Liu Wei-wei;Wang Chao;Tan Cheng-fu;...
期刊:
针灸推拿医学:英文版,2018年16(4):216-222 ISSN:1672-3597
通讯作者:
Xiao-rong Chang<&wdkj&>Jing Li
作者机构:
Hunan University of Chinese Medicine, Changsha, 410208;Liuyang Hospital of Chinese Medicine, Hunan, Liuyang, 410300;Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437;[Liu Mi] Hunan University of Chinese Medicine, Changsha, 410208 Liuyang Hospital of Chinese Medicine, Hunan, Liuyang, 410300;[Liu Yi; Liu Wei-wei; Wang Chao; Tan Cheng-fu; Liu Li; Peng Yan; Chang Xiao-rong; Yan Jie] Hunan University of Chinese Medicine, Changsha, 410208
通讯机构:
[Xiao-rong Chang] H;[Jing Li] Y;Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
摘要:
Objective: To observe the effect of point-moxibustion on gastrointestinal motility, mRNA and protein expressions of ghrelin and growth hormone secretagogue receptor 1a (GHSR-1a) in lateral septal nucleus of rats with diabetic gastroparesis (DGP), and to investigate the central regulatory mechanism of DGP treatment with point-moxibustion. Methods: Forty SPF-grade Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a point-moxibustion group, with 10 rats in each group. A DGP rat model was established by intraperitoneal injection of 2% streptozotocin (STZ) with 8-week irregular high-sugar and high-fat diet in the model group, the EA group and the point-moxibustion group; and rats in the blank group were injected intraperitoneally with 0.1 mmoL/L (pH 4.5) citric acid-sodium citrate buffer with 8-week normal diet. Eight weeks later, rats in the EA group were treated by EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); while rats in the point-moxibustion group were treated by point-moxibustion at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) for successive 15 d. Rats in the blank group and the model group were fixed as the control without intervention. After treatment, intestinal propulsion rate and gastric emptying rate were measured. The mRNA and protein expressions of ghrelin and GHSR-1a in the lateral septal nucleus were detected by real-time polymerase chain reaction (RT-PCR) and Western blot (WB). Results: Compared with the blank group, the intestinal propulsion rate and gastric emptying rate of the model group were significantly lower (both P<0.01); compared with the model group, the intestinal propulsion rate and gastric emptying rate of the EA group and the point-moxibustion group increased significantly (all P<0.05). The mRNA and protein expressions of ghrelin and GHSR-1a were lower in the model group than those in the blank group (all P<0.01). The mRNA and protein expressions of ghrelin and GHSR-1a were significantly higher in the EA group and the point-moxibustion group than those in the model group (all P<0.05). There were no statistically significant differences between the EA group and the point-moxibustion group (all P>0.05). Conclusion: Point-moxibustion at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) can increase the intestinal propulsion rate and gastric emptying rate of DGP rats, and promote the mRNA and protein expressions of ghrelin and GHSR-1a in the central nervous system. The mechanism may be related to the activation of ghrelin pathway in hypothalamic arcuate nucleus-lateral septal nucleus.
通讯机构:
[Zhou, YJ; Deng, X] C;Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China.
摘要:
A CuII-catalyzed radical annulation/C3-functionalization cascade of tryptamine derivatives with aryl ethylene is reported. The mild catalytic system enables the facile construction of 3a-benzoylmethylpyrrolidino[2,3-b]indolines with excellent chemo- and regioselectivities. Remarkably, this novel method utilizes earth-abundant and inexpensive cupric salt as the catalyst and air as the co-oxidant, rendering the process highly environmentally friendly and atom economic. Presumably, the reaction proceeds through CuII-initiated formation of pyrrolidino[2,3-b]indolines radical intermediate I, which is successively trapped by aryl ethylene and O2 to form the product. An 18O2-labeling experiment and several control experiments were designed to support the mechanistic proposal.
摘要:
Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes. Since autophagy has been reported to be related to melanin degradation, we also examined the activation of autophagy by ISL treatment in keratinocytes by measurement of autophagy-related proteins, ATG7, LC3 and p62. Moreover, si-ATG7-induced ATG7 knockdown and autophagy inhibitor 3-MA decreased LC3 II protein levels and increased PMEL17, p62 and melanin levels in HaCaT cells, which could be partially reversed by ISL treatment, indicating that autophagy participated in melanin degradation. The decreased p-AKT and p-mTOR proteins upon ISL treatment indicated the involvement of PI3K/AKT/mTOR signaling in ISL-induced melanin degradation. Taken together, we demonstrated that autophagy participates in ISL-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.