Chrysotherapeutics are under investigation as new or additional treatments for different types of cancers. In this study, gold complexes were investigated for their anticancer potential using Raman spectroscopy. The aim of the study was to determine whether Raman spectroscopy could be used for the characterization of metallodrug-induced cell death. Symptoms of cell death such as decreased peak intensities of proteins bonds and phosphodiester bonds found in deoxyribose nucleic acids were evident in the principal component analysis of the spectra. Vibrational bands around 761 cm−1 and 1300 cm−1 (tryptophan, ethanolamine group, and phosphatidylethanolamine) and 1720 cm−1 (ester bonds associated with phospholipids) appeared in the Raman spectra of cervical adenocarcinoma (HeLa) cells after metallodrug treatment. The significantly (p < 0.05, one way analysis of variance) increased intensity of phosphatidylethanolamine after metallodrug treatment could be a molecular signature of induced apoptosis since both the co-regulated phosphatidylserine and phosphatidylethanolamine are externalized during cell death. Treated cells had significantly higher levels of glucose and glycogen vibrational peaks, indicative of a survival mechanism of cancer cells under chemical stress. Cancer cells excrete chemotherapeutics to improve their chances of survival and utilize glucose to achieve this. Raman spectroscopy was able to monitor a survival strategy of cancer cells in the form of glucose uptake to alleviate chemical stress. Raman spectroscopy was invaluable in obtaining molecular information generated by biomolecules affected by anticancer metallodrug treatments and presents an alternative to less reproducible, conventional biochemical assays for cytotoxicity analyses.

1.
W. H.
Organisation
, Fact Sheet No. 380,
2013
.
2.
L. C.
Snyman
,
S. Afr. J. Obstet. Gynaecol.
19
,
2
(
2012
).
3.
Z. M.
Chirenje
,
Best Pract. Res. Clin. Obstet. Gynaecol.
19
,
269
(
2005
).
4.
A.
Amit
,
C. L.
Edwards
,
P.
Athey
, and
A. L.
Kaplan
,
Int. J. Gynecol. Cancer
11
,
78
(
2001
).
5.
E. R. T.
Tiekink
,
Inflammopharmacology
16
,
138
(
2008
).
6.
V.
Milacic
,
D.
Fregona
, and
Q. P.
Dou
,
Histol. Histopathol.
23
,
101
(
2008
).
7.
C.
Wetzel
,
P. C.
Kunz
,
M. U.
Kassack
,
A.
Hamacher
,
P.
Böhler
,
W.
Watjen
,
I.
Ott
,
R.
Rubbiani
, and
B.
Spingler
,
Dalton Trans.
40
,
9212
(
2011
).
8.
C.-M.
Che
,
R. W.-Y.
Sun
,
W.-Y.
Yu
,
C.-B.
Ko
,
N.
Zhu
, and
H.
Sun
,
Chem. Commun.
2003
(
14
),
1718
.
9.
P. N.
Fonteh
,
F. K.
Keter
, and
D.
Meyer
,
J. Inorg. Biochem.
105
,
1173
(
2011
).
10.
A. B.
Mullick
,
Y. M.
Chang
,
I.
Ghiviriga
,
K. A.
Abboud
,
W.
Tan
, and
A. S.
Veige
,
Dalton Trans.
42
,
7440
(
2013
).
11.
See supplementary material at http://dx.doi.org/10.1063/1.4896616 for details on the metallodrugs, flow cytometry zebra plots, raw Raman data, one way ANOVA, and Tukey multiple comparison test.
12.
C.
Matthaus
,
T.
Chernenko
,
J. A.
Newmark
,
C. M.
Warner
, and
M.
Diem
,
Biophys. J.
93
,
668
(
2007
).
13.
E.
Brauchle
,
S.
Thude
,
S. Y.
Brucker
, and
K.
Schenke-Layland
,
Sci. Rep.
4
,
4698
(
2014
).
14.
A.
Fujioka
,
K.
Terai
,
R. E.
Itoh
,
K.
Aoki
,
T.
Nakamura
,
S.
Kuroda
,
E.
Nishida
, and
M.
Matsuda
,
J. Biol. Chem.
281
,
8917
(
2006
).
15.
S.
Verrier
,
I.
Notingher
,
J. M.
Polak
, and
L. L.
Hench
,
Biopolymers
74
,
157
(
2004
).
16.
C.
Matthaus
,
S.
Boydston-White
,
M.
Miljkovic
,
M.
Romeo
, and
M.
Diem
,
Appl. Spectrosc.
60
,
1
(
2006
).
17.
G.
Perna
,
M.
Lasalvia
,
P.
D'Antonio
,
N.
L'Abbate
, and
V.
Capozzi
,
J. Raman Spectrosc.
42
,
603
(
2011
).
19.
Z.
Movasaghi
,
S.
Rehman
, and
I. U.
Rehman
,
Appl. Spectrosc. Rev.
42
,
493
(
2007
).
20.
T. J.
Moritz
,
D. S.
Taylor
,
D. M.
Krol
,
J.
Fritch
, and
J. W.
Chan
,
Biomed. Opt. Express
1
,
1138
(
2010
).
21.
I.
Notingher
,
S.
Verrier
,
S.
Haque
,
J.
Polak
, and
L.
Hench
,
Biopolymers
72
,
230
(
2003
).
22.
I.
Martin
,
V. I.
Poon
,
Z.
Petropoulos
,
S.
Harder
, and
J.
Lum
,
J. Cancer Res. Ther. Oncol.
1
,
1
(
2013
).
23.
A.
Zoladek
,
F.
Pascut
,
P.
Patel
, and
I.
Notingher
,
J. Raman Spectrosc.
42
,
251
(
2011
).
24.
I.
Notingher
,
J.
Selvakumaran
, and
L. L.
Hench
,
Biosens. Bioelectron.
20
,
780
(
2004
).
25.
Q.
Matthews
,
A.
Jirasek
,
J.
Lum
,
X.
Duan
, and
A. G.
Brolo
,
Appl. Spectrosc.
64
,
871
(
2010
).
26.
K. L.
Munro
,
K. R.
Bambery
,
E. A.
Carter
,
L.
Puskar
,
M. J.
Tobin
,
B. R.
Wood
, and
C. T.
Dillon
,
Vib. Spectrosc.
53
,
39
(
2010
).
27.
H.
Yao
,
Z.
Tao
,
M.
Ai
,
L.
Peng
,
G.
Wang
,
B.
He
, and
Y.
Li
,
Vib. Spectrosc.
50
,
193
(
2009
).
28.
C. M.
Krishna
,
G. D.
Sockalingum
,
R. A.
Bhat
,
L.
Venteo
,
P.
Kushtagi
,
M.
Pluot
, and
M.
Manfait
,
Anal. Bioanal. Chem.
387
,
1649
(
2007
).
29.
A.
Salman
,
E.
Shufan
,
L.
Zeiri
, and
M.
Huleihel
,
Biochim. Biophys. Acta
1830
,
2720
(
2013
).
30.
C.
Krafft
,
L.
Neudert
,
T.
Simat
, and
R.
Salzer
,
Spectrochim. Acta Part A
61
,
1529
(
2005
).
31.
R.
Chaurio
,
C.
Janko
,
L. E.
Munoz
,
B.
Frey
,
M.
Herrmann
, and
U. S.
Gaipl
,
Molecules
14
,
4892
(
2009
).
32.
J. H.
Stafford
and
P. E.
Thorpe
,
Neoplasia
13
,
299
(
2011
).
33.
K.
Emoto
,
N.
Toyama-Sorimachi
,
H.
Karasuyama
,
K.
Inoue
, and
M.
Umeda
,
Exp. Cell Res.
232
,
430
(
1997
).
34.
M.
Sanmarco
and
M.-C.
Boffa
,
Lupus
18
,
920
(
2009
).
35.
N. W.
Alcock
,
P.
Moore
,
P. A.
Lampe
, and
K. F.
Mok
Dalton Trans.
1982
,
207
(
1982
).
36.
M. J.
Calhorda
,
C.
Ceamanos
,
O.
Crespo
,
M. C.
Gimeno
,
A.
Laguna
,
C.
Larraz
,
P. D.
Vaz
, and
M. D.
Villacampa
,
Inorg. Chem.
49
,
8255
(
2010
).
37.
A. Y. F.
Elkhadir
, “
Phosphorous-nitrogen gold (I), palladium (II) and platinum (II) bimetallic complexes as potential antimalaria, antiHIV, antimycobateria, and anticancer agents
,” Ph.D. thesis (
University of Johannesburg
,
2014
).

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