PMID- 18603286
OWN - NLM
STAT- MEDLINE
DCOM- 20080909
LR  - 20220311
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 110
IP  - 3
DP  - 2008 Sep
TI  - Synergistic action of dietary phyto-antioxidants on survival and proliferation of 
      ovarian cancer cells.
PG  - 432-8
LID - 10.1016/j.ygyno.2008.05.001 [doi]
AB  - OBJECTIVES: A number of herbal dietary antioxidant supplements containing 
      Indole-3 Carbinol (I3C) and Resveratrol (RE) have been established as 
      anti-proliferative agents in cancer. These compounds have both similar as well as 
      unique molecular targeting profiles. The purpose of this study is to analyze 
      their mechanism of action when used individually and in combination in ovarian 
      cancer. METHODS: SK-OV-3 ovarian cancer cells were treated with various doses of 
      I3C, RE or I3C+RE. AlamarBlue dye assay was used to examine cell growth and 
      proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western 
      blot was performed to determine the expression of the genes associated with cell 
      cycle and apoptosis. CA-125, a functional marker of ovarian cancer, and nitric 
      oxide, were analyzed by ELISA. RESULTS: I3C or RE inhibited cell proliferation, 
      and caused cell contraction and apoptosis. Analysis of apoptosis-associated genes 
      revealed an inhibition of Retinoblastoma protein (Rb) and Survivin (SVV) gene 
      expression. This was accompanied by elevation of p21, a tumor suppressor. Cell 
      cycle was inhibited at both G1 and G2/M by individual treatments, and accentuated 
      by a combination. AlamarBlue assay revealed a clear synergistic action of I3C+RE. 
      CA125 was inhibited by either I3C or RE treatments. In contrast, basal nitric 
      oxide production was inhibited by I3C and I3C+RE but not RE alone. CONCLUSIONS: 
      This is the first evidence demonstrating the effects of I3C on ovarian cancer 
      cells and its synergism with RE. Based on this model, our data indicate that 
      combinations of compounds with different targeting properties will be more 
      effective in chemoprevention and/or chemotherapy of ovarian and possibly other 
      cancers.
FAU - Raj, Madhwa H G
AU  - Raj MH
AD  - Department of Ob-Gyn, School of Medicine, Louisiana State University Health 
      Sciences Center, New Orleans, Louisiana 70112, USA. mraj@lsuhsc.edu
FAU - Abd Elmageed, Zakaria Y
AU  - Abd Elmageed ZY
FAU - Zhou, Jing
AU  - Zhou J
FAU - Gaur, R L
AU  - Gaur RL
FAU - Nguyen, Lan
AU  - Nguyen L
FAU - Azam, Ghazala A
AU  - Azam GA
FAU - Braley, Patricia
AU  - Braley P
FAU - Rao, Prakash N
AU  - Rao PN
FAU - Fathi, Ismail M
AU  - Fathi IM
FAU - Ouhtit, Allal
AU  - Ouhtit A
LA  - eng
GR  - R01 CA081125/CA/NCI NIH HHS/United States
GR  - R25-CA47877/CA/NCI NIH HHS/United States
GR  - R03 CA091185-01A1/CA/NCI NIH HHS/United States
GR  - R03 CA091185/CA/NCI NIH HHS/United States
GR  - R03 CA091185-02S1/CA/NCI NIH HHS/United States
GR  - CA81125/CA/NCI NIH HHS/United States
GR  - CA91185/CA/NCI NIH HHS/United States
GR  - R25 CA047877/CA/NCI NIH HHS/United States
GR  - R03 CA091185-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080707
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Indoles)
RN  - 0 (Oxazines)
RN  - 0 (Stilbenes)
RN  - 0 (Xanthenes)
RN  - 1FN9YD6968 (resazurin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - C11E72455F (indole-3-carbinol)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Anticarcinogenic Agents/administration & dosage/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Antioxidants/administration & dosage/*pharmacology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Cycle/drug effects
MH  - Drug Synergism
MH  - Female
MH  - Humans
MH  - Indoles/administration & dosage/*pharmacology
MH  - Nitric Oxide/biosynthesis
MH  - Ovarian Neoplasms/*drug therapy/metabolism/pathology
MH  - Oxazines/chemistry
MH  - Resveratrol
MH  - Staining and Labeling/methods
MH  - Stilbenes/administration & dosage/*pharmacology
MH  - Xanthenes/chemistry
PMC - PMC2628811
MID - NIHMS70663
COIS- Conflict of Interest Statement The authors declare that there are no conflicts of 
      interest.
EDAT- 2008/07/08 09:00
MHDA- 2008/09/10 09:00
PMCR- 2009/09/01
CRDT- 2008/07/08 09:00
PHST- 2007/11/28 00:00 [received]
PHST- 2008/04/02 00:00 [revised]
PHST- 2008/05/01 00:00 [accepted]
PHST- 2008/07/08 09:00 [pubmed]
PHST- 2008/09/10 09:00 [medline]
PHST- 2008/07/08 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - S0090-8258(08)00353-3 [pii]
AID - 10.1016/j.ygyno.2008.05.001 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2008 Sep;110(3):432-8. doi: 10.1016/j.ygyno.2008.05.001. Epub 2008 
      Jul 7.