{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:03Z","timestamp":1786977963181,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2003,6,30]],"date-time":"2003-06-30T00:00:00Z","timestamp":1056931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Flavonoids were demonstrated to possess several biological effects including antitumor, antioxidant, and anti\u2010inflammatory activities in our previous studies. However, the effect of glycosylation on their biological functions is still undefined. In the present study, the apoptosis\u2010inducing activities of three structure\u2010related flavonoids including aglycone quercetin (QUE), and glycone rutin (RUT; QUE\u20103\u2010O\u2010rutinoside), and glycone quercitrin (QUI; QUE\u20103\u2010O\u2010rhamnoside) were studied. Both RUT and QUI are QUE glycosides, and possess rutinose and rhamnose at the C3 position of QUE, respectively. Results of the MTT assay showed that QUE, but not RUT and QUI, exhibits significant cytotoxic effect on HL\u201060 cells, accompanied by the dose\u2010 and time\u2010dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, apoptotic bodies, and an increase in hypodiploid cells by flow cytometry analysis. QUE, but not RUT or QUI, caused rapid and transient induction of caspase 3\/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP\u2010ribose) polymerase (PARP) and D4\u2010GDI proteins, and the appearance of cleaved caspase 3 fragments being detected in QUE\u2010 but not RUT\u2010 or QUI\u2010treated HL\u201060 cells. A decrease in the anti\u2010apoptotic protein, Mcl\u20101, was detected in QUE\u2010treated HL\u201060 cells, whereas other Bcl\u20102 family proteins including Bax, Bcl\u20102, Bcl\u2010XL, and Bag remained unchanged. The caspase 3 inhibitor, Ac\u2010DEVD\u2010FMK, but not the caspase 1 inhibitor, Ac\u2010YVAD\u2010FMK, attenuated QUE\u2010induced cell death. Results of DCHF\u2010DA assay indicate that no significant increase in intracellular peroxide level was found in QUE\u2010treated cells, and QUE inhibited the H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced intracellular peroxide level. Free radical scavengers\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl\u2010cysteine (NAC) and catalase showed no prevention of QUE\u2010induced apoptosis. In addition, QUE did not induce apoptosis in an mature monocytic cell line THP\u20101, as characterized by a lack of DNA ladders, caspase 3 activation, PARP cleavage, and an Mcl\u20101 decrease, compared with those in HL\u201060 cells. Our experiments provide evidence to indicate that the addition of rutinose or rhamnose attenuates the apoptosis\u2010inducing activity of QUE, and that the caspase 3 cascade but not free radical production is involved. J. Cell. Biochem. 89: 1044\u20131055, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jcb.10559","type":"journal-article","created":{"date-parts":[[2003,7,17]],"date-time":"2003-07-17T06:09:47Z","timestamp":1058422187000},"page":"1044-1055","source":"Crossref","is-referenced-by-count":113,"title":["Differential apoptosis\u2010inducing effect of quercetin and its glycosides in human promyeloleukemic HL\u201060 cells by alternative activation of the caspase 3 cascade"],"prefix":"10.1002","volume":"89","author":[{"given":"Shing\u2010Chuan","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Chou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng\u2010Lin","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woan\u2010Rouh","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,7,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00406-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90733-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.327550"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215077"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199612)17:4<224::AID-MC6>3.0.CO;2-D"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1999.tb01952.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199811)177:2<324::AID-JCP14>3.0.CO;2-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.1184"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01386-2"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-002-0346-6"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf010919h"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.4049\/jimmunol.157.2.500","article-title":"Defective Rho\u2010GTPase regulation by IL\u20101 beta\u2010converting enzyme\u2010mediated cleavage of D4\u2010GDP dissociation inhibitor","volume":"157","author":"Danley DE","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3470669"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00755-9"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.62.1428"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00260-8"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80386-X"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.22.749"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10154"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400515"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00748-1"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00876-0"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/20.4.733"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(1997)28\/29 <39::AID-JCB5>3.0.CO;2-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(83)90044-1"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00467-5"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520120127"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7533326"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00562-7"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","unstructured":"RodriguezJ LazebnikY.1999.Caspase 8 and apaf\u20101 form an active holoenzyme. 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