Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis

Julie Hanson Ostrander, Kevin J. Chalut, Michael G. Giacomelli, Adam Wax

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the light scattering signal reveals a change in the organization of subcellular structures that we interpret using fractal dimension (FD). The FD of subcellular structures in cells treated with paclitaxel and doxorubicin is observed to increase significantly compared with that of control cells as early as 1.5 and 3 hours after application, respectively. The FD is then found to decrease slightly at 6 hours postapplication for both agents only to increase again from 12 to 24 hours posttreatment when the observations ceased. The changes in structure appear over two time scales, suggesting that multiple mechanisms are evident in these early apoptotic stages. Indeed, quantitative image analysis of fluorescence micrographs of cells undergoing apoptosis verifies that the FD of 4′,6-diamidino-2-phenylindole-stained nuclear structures does not change significantly in cells until 12 hours after treatment, whereas that of MitoTracker stained mitochondria is seen to modulate as early as 3 hours after treatment. In contrast, cells receiving an increased dose of paclitaxel that induced G2-M arrest, but not apoptosis, only exhibited the early change in subcellular structure but did not show the later change associated with changes in nuclear substructure. These results suggest that a/LCI may have utility in detecting early apoptotic events for both clinical and basic science applications.

Original languageEnglish (US)
Pages (from-to)1199-1204
Number of pages6
JournalCancer Research
Volume69
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Fractals
Apoptosis
Light
Drug Therapy
Interferometry
Paclitaxel
MCF-7 Cells
Doxorubicin
Mitochondria
Therapeutics
Fluorescence

Cite this

Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis. / Ostrander, Julie Hanson; Chalut, Kevin J.; Giacomelli, Michael G.; Wax, Adam.

In: Cancer Research, Vol. 69, No. 3, 01.02.2009, p. 1199-1204.

Research output: Contribution to journalArticle

@article{a54ca1e5d6bf4b54b0d97b53d27d3a99,
title = "Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis",
abstract = "We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the light scattering signal reveals a change in the organization of subcellular structures that we interpret using fractal dimension (FD). The FD of subcellular structures in cells treated with paclitaxel and doxorubicin is observed to increase significantly compared with that of control cells as early as 1.5 and 3 hours after application, respectively. The FD is then found to decrease slightly at 6 hours postapplication for both agents only to increase again from 12 to 24 hours posttreatment when the observations ceased. The changes in structure appear over two time scales, suggesting that multiple mechanisms are evident in these early apoptotic stages. Indeed, quantitative image analysis of fluorescence micrographs of cells undergoing apoptosis verifies that the FD of 4′,6-diamidino-2-phenylindole-stained nuclear structures does not change significantly in cells until 12 hours after treatment, whereas that of MitoTracker stained mitochondria is seen to modulate as early as 3 hours after treatment. In contrast, cells receiving an increased dose of paclitaxel that induced G2-M arrest, but not apoptosis, only exhibited the early change in subcellular structure but did not show the later change associated with changes in nuclear substructure. These results suggest that a/LCI may have utility in detecting early apoptotic events for both clinical and basic science applications.",
author = "Ostrander, {Julie Hanson} and Chalut, {Kevin J.} and Giacomelli, {Michael G.} and Adam Wax",
year = "2009",
month = "2",
day = "1",
doi = "10.1158/0008-5472.CAN-08-3079",
language = "English (US)",
volume = "69",
pages = "1199--1204",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis

AU - Ostrander, Julie Hanson

AU - Chalut, Kevin J.

AU - Giacomelli, Michael G.

AU - Wax, Adam

PY - 2009/2/1

Y1 - 2009/2/1

N2 - We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the light scattering signal reveals a change in the organization of subcellular structures that we interpret using fractal dimension (FD). The FD of subcellular structures in cells treated with paclitaxel and doxorubicin is observed to increase significantly compared with that of control cells as early as 1.5 and 3 hours after application, respectively. The FD is then found to decrease slightly at 6 hours postapplication for both agents only to increase again from 12 to 24 hours posttreatment when the observations ceased. The changes in structure appear over two time scales, suggesting that multiple mechanisms are evident in these early apoptotic stages. Indeed, quantitative image analysis of fluorescence micrographs of cells undergoing apoptosis verifies that the FD of 4′,6-diamidino-2-phenylindole-stained nuclear structures does not change significantly in cells until 12 hours after treatment, whereas that of MitoTracker stained mitochondria is seen to modulate as early as 3 hours after treatment. In contrast, cells receiving an increased dose of paclitaxel that induced G2-M arrest, but not apoptosis, only exhibited the early change in subcellular structure but did not show the later change associated with changes in nuclear substructure. These results suggest that a/LCI may have utility in detecting early apoptotic events for both clinical and basic science applications.

AB - We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the light scattering signal reveals a change in the organization of subcellular structures that we interpret using fractal dimension (FD). The FD of subcellular structures in cells treated with paclitaxel and doxorubicin is observed to increase significantly compared with that of control cells as early as 1.5 and 3 hours after application, respectively. The FD is then found to decrease slightly at 6 hours postapplication for both agents only to increase again from 12 to 24 hours posttreatment when the observations ceased. The changes in structure appear over two time scales, suggesting that multiple mechanisms are evident in these early apoptotic stages. Indeed, quantitative image analysis of fluorescence micrographs of cells undergoing apoptosis verifies that the FD of 4′,6-diamidino-2-phenylindole-stained nuclear structures does not change significantly in cells until 12 hours after treatment, whereas that of MitoTracker stained mitochondria is seen to modulate as early as 3 hours after treatment. In contrast, cells receiving an increased dose of paclitaxel that induced G2-M arrest, but not apoptosis, only exhibited the early change in subcellular structure but did not show the later change associated with changes in nuclear substructure. These results suggest that a/LCI may have utility in detecting early apoptotic events for both clinical and basic science applications.

UR - http://www.scopus.com/inward/record.url?scp=59149095069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59149095069&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-3079

DO - 10.1158/0008-5472.CAN-08-3079

M3 - Article

C2 - 19141640

AN - SCOPUS:59149095069

VL - 69

SP - 1199

EP - 1204

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 3

ER -