https://scholars.lib.ntu.edu.tw/handle/123456789/544261
Title: | Resistance to paclitaxel is proportional to cellular total antioxidant capacity | Authors: | Ramanathan B. Jan K.-Y. Chen C.-H. Hour T.-C. HONG-JENG YU YEONG-SHIAU PU |
Issue Date: | 2005 | Journal Volume: | 65 | Journal Issue: | 18 | Start page/Pages: | 8455-8460 | Source: | Cancer Research | Abstract: | Paclitaxel, one of the most commonly prescribed chemotherapeutic agents, is active against a wide spectrum of human cancer. The mechanism of its cytotoxicity, however, remains controversial. Our results indicate that paclitaxel treatment increases levels of superoxide, hydrogen peroxide, nitric oxide (NO), oxidative DNA adducts, G2-M arrest, and cells with fragmented nuclei. Antioxidants pyruvate and selenium, the NO synthase inhibitor Nω-nitro-L-arginine methyl ester, and the NO scavenger manganese (III) 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3- oxide all decreased paclitaxel-mediated DNA damage and sub-G1 cells. In contrast, the glutamylcysteine synthase inhibitor buthionine sulfoximine (BSO) and the superoxide dismutase (SOD) inhibitor 2-methoxyestradiol (2-ME) increased the sub-G1 fraction in paclitaxel-treated cells. These results suggest that reactive oxygen and nitrogen species are involved in paclitaxel cytotoxicity. This notion is further supported with the observation that concentrations of paclitaxel required to inhibit cell growth by 50% correlate with total antioxidant capacity. Moreover, agents such as arsenic trioxide (As2O3), BSO, 2-ME, PD98059, U0126 [mitogen-activated protein/extracellular signal-regulated kinase inhibitors], and LY294002 (phosphatidylinositol 3-kinase/Akt inhibitor), all of which decrease clonogenic survival, also decrease the total antioxidant capacity of paclitaxel-treated cells, regardless whether they are paclitaxel sensitive or paclitaxel resistant. These results suggest that paclitaxel chemosensitivity may be predicted by taking total antioxidant capacity measurements from clinical tumor samples. This, in turn, may then improve treatment outcomes by selecting out potentially responsive patients. ?2005 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-24944486664&doi=10.1158%2f0008-5472.CAN-05-1162&partnerID=40&md5=f7a2bc7e32e220ef671ca45d186e1add https://scholars.lib.ntu.edu.tw/handle/123456789/544261 |
ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-05-1162 | SDG/Keyword: | 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; 2 (2 amino 3 methoxyphenyl)chromone; 2 (4 carboxyphenyl) 4,4,5,5 tetramethylimidazoline 1 oxyl 3 oxide; 2 morpholino 8 phenylchromone; arsenic trioxide; hydrogen peroxide; mitogen activated protein kinase inhibitor; n(g) nitroarginine methyl ester; nitric oxide; nitrogen; paclitaxel; phosphatidylinositol 3 kinase inhibitor; pyruvic acid; reactive oxygen metabolite; selenium; superoxide; antioxidant activity; article; cell cycle G1 phase; cell cycle G2 phase; cell growth; controlled study; cytotoxicity; DNA adduct; DNA damage; human; human cell; mitosis; priority journal; Antineoplastic Agents, Phytogenic; Antioxidants; Breast Neoplasms; Cell Division; Cell Growth Processes; Cell Nucleus; Drug Resistance, Neoplasm; G2 Phase; Humans; Nitric Oxide; Paclitaxel; Reactive Oxygen Species [SDGs]SDG3 |
Appears in Collections: | 醫學系 |
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