Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Bioanalytical chemistry of microtubule stabilizers: proteomic changes induced by MT stabilizers in non-small cell lung cancer (NSCLC) cells

Lu, Ying (2005) Bioanalytical chemistry of microtubule stabilizers: proteomic changes induced by MT stabilizers in non-small cell lung cancer (NSCLC) cells. Master's Thesis, University of Pittsburgh. (Unpublished)

Primary Text

Download (1MB) | Preview


Lung cancers are typically malignant tumors found in one or both lungs. These cancers usually form from cells that line the airways and nearby glands because it is these cells that come into contact with the air we breathe and the many carcinogens that are contained within it. In the US, there are approximately 413,000 people with lung cancer at any given time. Non-small cell lung cancer accounts for about 80% of all lung cancer cases. So far, the diagnosis of lung cancer relies significantly on physical examination. This late detection usually results in a high probability of metastasis and consequently high mortality. Therefore, as the second most common cancer diagnosed in US, the earlier detection and therefore treatment of lung cancer has been one of the primary goals of researchers. Paclitaxel (Taxol), a microtubule (MT) stabilizing agent originally noted to be useful against ovarian and breast cancers, has recently been found to have clinical utility in the treatment of lung cancer. A variety of structurally diverse MT stabilizers have been discovered over the past decade. These agents include discodermolide, laulimalide and dictyostatin, originally isolated from marine sponges, epothilones, originally isolated from the broth of fermenting soil bacteria, and eleutherobin, first found from soft corals. Many reports show that these agents have activity, all in vitro and some in vivo, against human cancers. Even though the binding site of laulimalide on MTs differs from the other MT stabilizers, these drugs have a common feature in that their working mechanism includes the enhancement of tubulin assembly into hyperstable microtubules, the arrest of cells in G2/M phase of the cell cycle, and the induction of apoptosis. As the MT stabilizing action well proceeds the induction of apoptosis, there obviously must be some changes in the affected cells' proteome, including both expression and post-translational changes, which are a result of MT stabilization and represent early signals that lead to activation of the apoptosis cascade. This hypothesis is partially supported by a few reports in which H292 and H157 cells were examined before and after (6 to 24 hours) different treatment times with MT stabilizers. Significant changes in the proteome of carcinoma cells treated with MT stabilizers are apparent after a long time of treatment (72 hours). Few proteomic changes have yet to be detected in the shorter treatment times. This lack of data in the short treatment times is the impetus for the current project. The goal of the project is to detect and characterize the earlier proteomic changes of NSCLC cells after treatment with MT stabilizing agents. In this study, H460 human non-small cell lung cancer (NSCLC) cell line was selected and different MT stabilizing agents, including paclitaxel, discodermolide, dictyostatin-1, and laulimalide were and would be tested in a 6-hour treatment time. 2-D DiGE was employed instead of traditional 2DE and MALDI-TOF was used in protein identification. The up-to-date results showed that EEF1G was over-expressed and stathmin was decreased expressed in the discodermolide-treated H460 cancer cells with respect to their DMSO-treated control. It is expected that a more detailed understanding of NSCLC cells' response to MT stabilizers in combination with efforts toward earlier detection of the disease will allow for more rational decision-making in the clinical treatment of the disease.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDay, Billy Wbday@pitt.eduBDAY
Committee MemberKoide, Kazunorikoide@pitt.eduKOIDE
Committee MemberWeber, Stevesweber@pitt.eduSWEBER
Date: 18 October 2005
Date Type: Completion
Defense Date: 13 April 2005
Approval Date: 18 October 2005
Submission Date: 15 May 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: differential gel electrophoresis; microtubule stabilizer; non-small cell lung cancer cells; microtubule; proteomics
Other ID:, etd-05152005-104923
Date Deposited: 10 Nov 2011 19:44
Last Modified: 15 Nov 2016 13:43


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item