東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back to Search results for [ null ]

Switch To: Labeled | MARC Mode | ISBD

Intrinsic oxidative stress in cancer...

Hileman, Elizabeth Anne Oldham.

Linked to FindBook

Google Book

Amazon

博客來

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents./
Author:	Hileman, Elizabeth Anne Oldham.
Description:	168 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0646.
Contained By:	Dissertation Abstracts International64-02B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3081465

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents.
Hileman, Elizabeth Anne Oldham.

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents. - 168 p.

Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0646.

Thesis (Ph.D.)--The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, 2003.

A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2<super>·− </super>), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2<super>·− </super> is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2<super>·−</super> and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2<super>·−</super>, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells.Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents.
LDR:03595nam 2200277 a 45 001 929778
005 20110427
008 110427s2003 eng d
035 $a (UnM)AAI3081465
035 $a AAI3081465
040 $a UnM $c UnM
100 1 $a Hileman, Elizabeth Anne Oldham. $3 1253264
245 1 0 $a Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS-generating agents.
300 $a 168 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0646.
500 $a Supervisor: Peng Huang.
502 $a Thesis (Ph.D.)--The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, 2003.
520 $a A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2<super>·− </super>), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2<super>·− </super> is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2<super>·−</super> and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2<super>·−</super>, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells.
590 $a School code: 2034.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
690 $a 0487
690 $a 0992
710 2 0 $a The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences. $3 1251166
773 0 $t Dissertation Abstracts International $g 64-02B.
790 $a 2034
790 1 0 $a Huang, Peng, $e advisor
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3081465