Friend With Lung Cancer Newly Diagnosed

Emstar1892

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fasting for long periods of time sometimes reverses a lot of unkown untreatable issues. works pretty good on cancer too. just drink water and sleep good for 40 days, it is in the bible!


Agreed, but again, it's incredibly hard for people who are already weak. I used to fast intermittently a few years back and did amazing. Now, if I don't eat for more than 10 hours, my cortisol and blood pressure drop to the point of collapse - and i don't even have cancer!
 

Travis

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And avoiding PUFA seems essential. The rat experiment linked above is telling. Perhaps it can be kept in-check on a fat-free diet alone.

This lady used to have breast cancer and she wins marathons in her age and sex group.
 

InChristAlone

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I think the most important part of any treatment is to have supportive people around you, ones who say that you are doing the right thing, so no matter the outcome there are no regrets. Sadly we all have to die someday, some pass over sooner than others, so make the journey one full of love for yourself. The people who seem to do the best in life seem to be ones who are grateful to be alive. I think a part of getting cancer is years of not caring for yourself, being a doormat, life full of fears, anxieties and stresses. Maybe the gerson therapy works for people who say 'I'm going to love myself enough to get better'.
 

Travis

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Velve921

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Dr. Peat wrote me this:

Lung cancer cells produce increased amounts of some things that promote abnormal growth, and some of these can be inhibited by common harmless materials. The effects of adenosine and (leaked) ATP are inhibited by caffeine, prostaglandins are inhibited by aspirin and pregnenolone, estrogen by progesterone, aromatase inhibitors, orange juice and cooked mushrooms, histamine and serotonin by antihistamines, cyproheptadine, nitric oxide by tetracycline, progesterone, agmatine, etc. Emodin, in cascara, blocks various things in lung cancer, and its laxative effect helps to lower nitric oxide, histamine, and serotonin.

1. Front Immunol. 2016 Mar 29;7:109.
A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment.
Ohta A(1).
(1)Center for Drug Discovery, Northeastern University , Boston, MA , USA.
Within tumors, some areas are less oxygenated than others. Since their home
ground is under chronic hypoxia, tumor cells adapt to this condition by
activating aerobic glycolysis; however, this hypoxic environment is very harsh
for incoming immune cells. Deprivation of oxygen limits availability of energy
sources and induces accumulation of extracellular adenosine in tumors.
Extracellular adenosine, upon binding with adenosine receptors on the surface of
various immune cells, suppresses pro-inflammatory activities.
In addition,
signaling through adenosine receptors upregulates a number of anti-inflammatory
molecules and immunoregulatory cells, leading to the establishment of a
long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine,
tumors can discourage antitumor immune responses no matter how the response was
induced, whether it was spontaneous or artificially introduced with a therapeutic
intention. Preclinical studies have shown the significance of adenosine in tumor
survival strategy by demonstrating tumor regression after inactivation of
adenosine receptors,
inhibition of adenosine-producing enzymes, or reversal of
tissue hypoxia. These promising results indicate a potential use of the
inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.

Adenosine A2A Receptor: A Prognosis Marker For Lung Cancer
Tech ID: 08-11
Summary
The role of angiogenesis in tumor survival and metastasis is now well recognized. Hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha are both known to induce angiogenesis by upregulating a common set of cytokines, including VEGF, but only the activation of HIF-2alpha has been associated with poor prognosis in lung cancer. However, since HIF-2alpha is highly labile, it is a poor candidate for a biomarker.
Scientists at National Jewish Health have discovered that the receptor Adenosine A2A (ADORA2A) is expressed only in response to HIF-2alpha activation and more importantly that the expression of ADORA2A is increased in later stage lung tumors.
This receptor could therefore be used as a prognosis marker for lung cancer as well as a potential new target for an anti-angiogenic approach to treating lung cancer.
Potential Applications
A biomarker for HIF-2alpha activation and therefore for poor prognosis in lung cancer.
A target for anti-angiogenic therapy in lung cancer

Cancer Biol Ther. 2013 Sep;14(9):860-8.
Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth.
Mediavilla-Varela M1, Luddy K1, Noyes D1, Khalil FK2, Neuger AM3, Soliman H4, Antonia SJ5.
Recently it has become clear that the cost associated with the Warburg effect, which is inefficient production of ATP, is offset by selective advantages that are produced by resultant intracellular metabolic alterations. In fact tumors may be addicted to the Warburg effect. In addition these alterations result in changes in the extracellular tumor microenvironment that can also produce selective advantages for tumor cell growth and survival. One such extracellular alteration is increased adenosine concentrations that have been shown to impair T cell mediated rejection and support angiogenesis. The expression of the A2A receptor in non-small cell cancer (NSCLC) tissues, cell lines and cancer associated fibroblasts (CAF) was determined by performing immunohistrochemistry and immunoblot analysis. The efficacy of the A2A receptor antagonists in vivo was evaluated in a PC9 xenograft model. To determine the mode of cell death induced by A2A receptor antagonists flow cytometry, immunoblot, and cytotoxic analysis were performed. We found that a significant number of lung adenocarcinomas express adenosine A2A receptors. Antagonism of these receptors impaired CAF and tumor cell growth in vitro and inhibited human tumor xenograft growth in mice. These observations add to the rationale for testing adenosine A2A receptor antagonists as anticancer therapeutics. Not only could there be prevention of negative signaling in T cells within the tumor microenvironment and inhibition of angiogenesis, but also an inhibitory effect on tumor-promoting, immunosuppressive CAFs and a direct inhibitory effect on the tumor cells themselves.
Biochim Biophys Acta. 2011 Jun;1807(6):726-34.

Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and
increases reactive oxygen species resulting in ATP depletion and cell death in
human glioblastoma cells.
Pike LS(1), Smift AL, Croteau NJ, Ferrick DA, Wu M.
(1)Seahorse Bioscience, North Billerica, MA 01862, USA.
Normal differentiated cells rely primarily on mitochondrial oxidative
phosphorylation to produce adenosine triphosphate (ATP) to maintain their
viability and functions by using three major bioenergetic fuels: glucose,
glutamine and fatty acids. Many cancer cells, however, rely on aerobic glycolysis
for their growth and survival, and recent studies indicate that some cancer cells
depend on glutamine as well. This altered metabolism in cancers occurs through
oncogene activation or loss of tumor suppressor genes in multiple signaling
pathways, including the phosphoinositide 3-kinase and Myc pathways. Relatively
little is known, however, about the role of fatty acids as a bioenergetic fuel in
growth and survival of cancer cells. Here, we report that human glioblastoma
SF188 cells oxidize fatty acids and that inhibition of fatty acid β-oxidation by
etomoxir, a carnitine palmitoyltransferase 1 inhibitor, markedly reduces cellular
ATP levels and viability. We also found that inhibition of fatty acid oxidation
controls the NADPH level. In the presence of reactive oxygen species scavenger
tiron, however, ATP depletion is prevented without restoring fatty acid
oxidation. This suggests that oxidative stress may lead to bioenergetic failure
and cell death. Our work provides evidence that mitochondrial fatty acid
oxidation may provide NADPH for defense against oxidative stress and prevent ATP
loss and cell death.

PLoS One. 2009 Sep 15;4(9):e7033.
Oxygen consumption can regulate the growth of tumors, a new perspective on the
Warburg effect.
Chen Y(1), Cairns R, Papandreou I, Koong A, Denko NC.
(1)Division of Radiation and Cancer Biology, Department of Radiation Oncology,
Stanford University School of Medicine, Stanford, California, USA.
BACKGROUND: The unique metabolism of tumors was described many years ago by Otto
Warburg, who identified tumor cells with increased glycolysis and decreased
mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per
glucose molecule than mitochondrial oxidative phosphorylation, so in terms of
energy production, it is unclear how increasing a less efficient process provides
tumors with a growth advantage.
METHODS/FINDINGS: We carried out a screen for loss of genetic elements in
pancreatic tumor cells that accelerated their growth as tumors, and identified
mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells
decreased mitochondrial activity, and increased glycolysis, but paradoxically,
decreased cellular growth in vitro. Following Warburg's observations, this
mutation causes decreased mitochondrial function, compensatory increase in
glycolysis and accelerated growth in vivo. Likewise, knockdown of either
mitochondrial ribosomal protein L12 (MRPL12) or cytochrome oxidase had a similar
effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1)
increased oxygen consumption and decreased tumor growth. Finally, treatment of
tumor bearing animals with dichloroacetate (DCA) increased pyruvate consumption
in the mitochondria, increased total oxygen consumption, increased tumor hypoxia
and slowed tumor growth.

CONCLUSIONS: We interpret these findings to show that non-oncogenic genetic
changes that alter mitochondrial metabolism can regulate tumor growth through
modulation of the consumption of oxygen, which appears to be a rate limiting
substrate for tumor proliferation.

Acta Pharmacol Sin. 2016 May 2.
Dexamethasone suppresses the growth of human non-small cell lung cancer via
inducing estrogen sulfotransferase and inactivating estrogen.
Wang LJ(1), Li J(1), Hao FR(1), Yuan Y(1), Li JY(1), Lu W(2,)(1), Zhou TY(2,)(1).
(1)Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking
University, Beijing 100191, China. (2)State Key Laboratory of Natural and
Biomimetic Drugs, Peking University, Beijing 100191, China.
AIM: Dexamethasone (DEX) is a widely used synthetic glucocorticoid, which has
shown anti-cancer efficacy and anti-estrogenic activity. In this study we
explored the possibility that DEX might be used as an endocrine therapeutic agent
to treat human non-small cell lung cancer (NSCLC).
METHODS: The viability and proliferation of human NSCLC cell lines A549 and H1299
were assessed in vitro. Anti-tumor action was also evaluated in A549 xenograft
nude mice treated with DEX (2 or 4 mg·kg(-1)·d(-1), ig) or the positive control
tamoxifen (50 mg·kg(-1)·d(-1), ig) for 32 d. The expression of estrogen
sulfotransferase (EST) in tumor cells and tissues was examined. The intratumoral
estrogen levels and uterine estrogen responses were measured.
RESULTS: DEX displayed mild cytotoxicity to the NSCLC cells (IC50 >500 μmol/L)
compared to tamoxifen (IC50 <50 μmol/L), but it was able to inhibit the cell
proliferation at low micromolar ranges. Furthermore, DEX (0.1-10 μmol/L)
dose-dependently up-regulated EST expression in the cells, and inhibited the cell
migration in vitro. Triclosan, a sulfation inhibitor, was able to diminish
DEX-caused inhibition on the cell viability. In A549 xenograft nude mice, DEX or
tamoxifen administration remarkably suppressed the tumor growth. Moreover, DEX
administration dose-dependently increased EST expression in tumor tissues, and
reduced intratumoral estrogen levels as well as the volumes and weights of uteri.
CONCLUSION: DEX suppresses the growth of A549 xenograft tumors via inducing EST
and decreasing estradiol levels in tumor tissues, suggesting that DEX may be used
as anti-estrogenic agent for the treatment of NSCLC.

Am J Transl Res. 2016 Jan 15;8(1):81-97. eCollection 2016.
Prognostic significance of aromatase and estrogen receptor beta expression in
EGFR wild-type lung adenocarcinoma.
Tanaka K(1), Shimizu K(1), Kakegawa S(1), Ohtaki Y(1), Nagashima T(1), Kaira
K(2), Horiguchi J(1), Oyama T(3), Takeyoshi I(1).
(1)Department of Thoracic and Visceral Organ Surgery, Graduate School of
Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
(2)Department of Medicine and Molecular Science, Graduate School of Medicine,
Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
(3)Department of Division of Diagnostic Pathology, Graduate School of Medicine,
Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
OBJECTIVES: Based on recent findings of aromatase and estrogen receptor beta
(ERβ) expression in non-small-cell lung cancer, we assessed the
clinicopathological and prognostic significance of aromatase and ERβ expression
and their relationship to epidermal growth factor receptor (EGFR) mutation in
lung adenocarcinoma.
MATERIALS AND METHODS: We evaluated 150 resected primary lung adenocarcinoma
specimens. Expression of aromatase, ERα, ERβ, progesterone receptor (PR), and
human epidermal growth factor receptor 2 (HER2) was evaluated by immunostaining,
and EGFR and KRAS mutations were analyzed. Overall survival (OS) and
recurrence-free survival (RFS) were calculated using the Kaplan-Meier method.
RESULTS: Expression of aromatase, ERα, ERβ, PR, and HER2 was detected in 88.0%,
1.3%, 79.3%, 2.7%, and 39.3% of specimens, respectively. In patients with EGFR
wild-type lung adenocarcinoma, high aromatase expression was an independent
predictor of poor OS (hazard ratio
=2.638; 95% confidence interval [CI],
1.173-5.936; P=.019) and RFS (HR=2.505; 95% CI, 1.154-5.434; P=.020). Positive
ERβ expression was also an independent predictor of poor RFS (HR=4.013; 95% CI,
1.219-13.207; P=.022). Furthermore, high aromatase expression was a significant
predictor of poor survival only in females (OS, P=.010; RFS, P=.007), whereas
positive ERβ expression was an important predictor of poor survival only in males
(OS, P=.073; RFS, P=.051). No prognostic significance was observed in patients
with EGFR mutations.
CONCLUSIONS: Our findings suggest that EGFR wild-type lung adenocarcinoma is an
estrogen-dependent carcinoma, and aromatase expression and ERβ expression are
potent prognostic markers for EGFR wild-type lung adenocarcinoma.

Front Biosci (Landmark Ed). 2009 Jan 1;14:2285-92.
Expression of aromatase CYP19 and its relationship with parameters in NSCLC.
Oyama T(1), Kagawa N, Sugio K, Uramoto H, Hatano O, Harada N, Kaneko K, Kawamoto
T, Yasumoto K.
(1)Second Department of Surgery and Department of Environmental Health,
University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
[email protected]
Human aromatase (CYP19) responsible for the conversion of androgens to estrogens
is expressed not only in gonads and adrenals but also in many other tissues,
including normal lungs and lung cancers. To investigate the involvement of CYP19
in lung cancer development, purified CYP19 protein and antibody are required. In
this study, we have developed an efficient expression method of human aromatase
in E. coli (>1000 nmol/L culture). The protein purified from E. coli was used to
raise an antibody against the human CYP19 in rabbits. The resulting antibody
showed a high titer judged by ELISA, which allowed us to determine the expression
of CYP19 in non-small cell lung cancer (NSCLC). Of 78 NSCLC specimens from
Japanese patients, 50 (64%) NSCLC aberrantly expressed CYP19. This CYP19
expression in NSCLC was independent of any clinical and pathological parameters
as well as the expression of other P450s, except tumor stage. The results suggest
that the aromatase inhibitors might be useful for the management of non-small
cell lung cancer in postmenopausal women.

Ann N Y Acad Sci. 2009 Feb;1155:194-205.
Targeting aromatase and estrogen signaling in human non-small cell lung cancer.
Márquez-Garbán DC(1), Chen HW, Goodglick L, Fishbein MC, Pietras RJ.
(1)University of California School of Medicine, Department of Medicine, Division
of Hematology-Oncology, Los Angeles, California 90095-1678, USA.
[email protected]
Lung cancer has become increasingly common in women, and gender differences in
the physiology and pathogenesis of the disease have suggested a role for
estrogens. In the lung recent data have shown local production of estrogens from
androgens via the action of aromatase enzyme and higher levels of estrogen in
tumor tissue as compared with surrounding normal lung tissue. High levels of
aromatase expression are also maintained in metastases as compared with primary
tumors. Consistent with these findings, clinical studies suggest that aromatase
expression may be a useful predictive biomarker for prognosis in the management
of non-small cell lung cancer (NSCLC), the most common form of lung malignancy.
Low levels of aromatase associate with a higher probability of long-term survival
in older women with early stage NSCLC. Treatment of lung NSCLC xenografts in vivo
with an aromatase inhibitor (exemestane) alone or combined with standard
cisplatin chemotherapy elicits a significant reduction in tumor progression as
compared to paired controls. Further, lung cancer progression is also governed by
complex interactions between estrogen and growth factor signaling pathways to
stimulate the growth of NSCLC as well as tumor-associated angiogenesis. We find
that combination therapy with the multitargeted growth factor receptor inhibitor
vandetanib and the estrogen receptor antagonist fulvestrant inhibit tumor growth
more effectively than either treatment administered alone. Thus, incorporation of
antiestrogen treatment strategies in standard antitumor therapies for NSCLC may
contribute to improved patient outcome, an approach that deserves to be tested in
clinical trials.

Acta Pharmacol Sin. 2004 Jun;25(6):812-6.
Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis.
Xiang Y(1), Ma B, Li T, Gao JW, Yu HM, Li XJ.
(1)Department of Pharmacology, School of Basic Medical Sciences, Peking
University, Beijing 100083, China.
AIM: To study effects of acetazolamide on aquaporin-1 (AQP(1)) protein expression
and angiogenesis.
METHODS: Establishing Lewis-lung-carcinoma model, the localization of AQP(1) in
tumor tissues was investigated by immunohistochemical methods; The biological
activity of acetazolamide was detected by endothelial cells proliferation test
(MTT) assay and chorioallantoic membrane (CAM) vascular inhibition test.
RESULTS: Immunohistochemical localization of AQP(1) in mice tumor was labeled in
capillaries, post capillary venules endothelial cells. After being treated with
acetazolamide, the number of capillaries and post capillary venules was
significantly decreased in tumor tissue. Acetazolamide showed significant
inhibitory effect on angiogenesis in CAM and endothelial cell proliferation.
CONCLUSION: Acetazolamide might be identified and developed as one of potential
lead compounds for a new therapeutic intervention in inhibiting cancer
angiogenesis.

1. Inflammopharmacology. 2014 Apr;22(2):127-34.
Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through
inducing apoptosis.
Li WY(1), Ng YF, Zhang H, Guo ZD, Guo DJ, Kwan YW, Leung GP, Lee SM, Yu PH, Chan
SW.
(1)Department of Applied Biology and Chemical Technology, The Hong Kong
Polytechnic University, Hong Kong, China.
This study investigated the mechanism of the cytotoxic effect of emodin, an
active anthraquinone, on human lung adenocarcinoma A549 cells. In vitro growth
inhibition and suppression on colony forming were used to evaluate the effects of
emodin on A549 cells. Emodin's ability in changing the expressions of
apoptosis-related genes was studied by real-time RT-PCR. Emodin could
significantly inhibit the growth of A549 cells with IC50 = 16.85 μg/ml (~60 μM).
It also concentration dependently inhibited the colony-forming ability of A549
cells with IC50 = 7.60 μg/ml (~30 μM). Hallmarks of apoptosis, such as
single-strand DNA breakage and DNA fragmentation, were observed in A549 cells
treated with emodin. Emodin (72 h) treatment could up-regulate the gene
expression of FASL (p < 0.05) and down-regulate the gene expression of C-MYC (p <
0.01), but induce no significant changes in the gene expressions of MCL1, GAPDH,
BAX and CCND1. These results suggest that emodin could induce growth inhibition
and apoptosis in A549 cells through modifying the extrinsic apoptotic pathways
and the induction of cell cycle arrest.

2. Cancer Lett. 2013 Dec 1;341(2):139-49. doi: 10.1016/j.canlet.2013.08.023. Epub
2013 Aug 17.
Targeted abrogation of diverse signal transduction cascades by emodin for the
treatment of inflammatory disorders and cancer.
Shrimali D(1), Shanmugam MK, Kumar AP, Zhang J, Tan BK, Ahn KS, Sethi G.
(1)Department of Pharmacology, Yong Loo Lin School of Medicine, National
University of Singapore, Singapore 117597, Singapore.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural occurring
anthraquinone derivative isolated from roots and barks of numerous plants, molds,
and lichens. It is found as an active ingredient in different Chinese herbs
including Rheum palmatum and Polygonam multiflorum, and has diuretic,
vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory,
and anti-cancer effects. The anti-inflammatory effects of emodin have been
exhibited in various in vitro as well as in vivo models of inflammation including
pancreatitis, arthritis, asthma, atherosclerosis and glomerulonephritis. As an
anti-cancer agent, emodin has been shown to suppress the growth of various tumor
cell lines including hepatocellular carcinoma, pancreatic, breast, colorectal,
leukemia, and lung cancers. Emodin is a pleiotropic molecule capable of
interacting with several major molecular targets including NF-κB, casein kinase
II, HER2/neu, HIF-1α, AKT/mTOR, STAT3, CXCR4, topoisomerase II, p53, p21, and
androgen receptors which are involved in inflammation and cancer. This review
summarizes reported anti-inflammatory and anti-cancer effects of emodin, and
re-emphasizes its potential therapeutic role in the treatment of inflammatory
diseases and cancer.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

3. Immunopharmacol Immunotoxicol. 2013 Apr;35(2):307. doi:
10.3109/08923973.2013.766802.
Emodin: inhibitory effects on growth in malignant tumors.
Kapoor S.
Comment on
Immunopharmacol Immunotoxicol. 2012 Oct;34(5):768-78.

4. J Appl Toxicol. 2014 Jan;34(1):95-104. doi: 10.1002/jat.2838. Epub 2012 Dec 5.
Exploration of effects of emodin in selected cancer cell lines: enhanced growth
inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like
conditions.
Masaldan S(1), Iyer VV.
(1)Centre for Bio-Separation Technology, VIT University, Vellore, 632014, Tamil
Nadu, India.
This study explores the link between the antiproliferative activity of emodin
through the generation of reactive oxygen species (ROS) in various cancer cell
lines and the expression of the androgen receptor (AR) in the prostate cancer
cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as
the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in
the above prostate cancer cells and the nonprostate cell lines A549 (lung),
HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among
all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549.
The mechanism of cytotoxicity of emodin was postulated to be the widely reported
ROS generation, based on the observations of poor in vitro radical-scavenging
activity and increased growth inhibition of emodin by ascorbic acid (AA)
pre-treatment owing to the additive effects of ROS generation by emodin and
pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and
hypoxia-like conditions (simulated by CoCl(2)) and LRP1 under normoxia. Emodin
upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even
more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP
and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like
conditions along with growth inhibition by emodin, suggests that emodin may be a
useful therapeutic option against androgen-sensitive prostate cancer and other
such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels
to allow the uptake of emodin and/or any other accompanying therapeutic agents by
LRP1.
Copyright © 2012 John Wiley & Sons, Ltd.



5. Asian Pac J Cancer Prev. 2012;13(4):1505-10.
Effects of emodin extracted from Chinese herbs on proliferation of non-small cell
lung cancer and underlying mechanisms.
He L(1), Bi JJ, Guo Q, Yu Y, Ye XF.
(1)Department of Pathology, Institute of Neuroscience, Chongqing Key Laboratory
of Neurobiology, Chongqing Medical University, Chongqing, China.
To aim of this was to observe emodin-mediated cytotoxicity and its influence on
Rad51 and ERCC1 expressionin non-small cell lung cancer (NSCLC). NSCLC cells were
cultured in vitro with emodin at various concentrations (0, 25, 50, 75 and 100
μmol/L) for 48 h and the proliferation inhibition rate was determined by the MTT
method. Then, NSCLC were treated with emodin (SK-MES-1 40 μmol/L, A549 70 μmol/L)
or 20 μmol/L U0126 (an ERK inhibitor) for 48 h, or with various concentrations of
emodin for 48 h and the protein and mRNA expressions of ERCC1 and Rad51 were
determined by RT-PCR and Western blot assay, respectively. Emodin exerted a
suppressive effect on the proliferation of NSCLC in a concentration dependent
manner. Protein and mRNA expression of ERCC1 and Rad51 was also significantly
decreased with the dose. Vacuolar degeneration was observed in A549 and SK-MES-1
cell lines after emodin treatment by transmission electron microscopy. Emodin may
thus inhibited cell proliferation in NSCLC cells by downregulation ERCC1 and
Rad51.


6. Immunopharmacol Immunotoxicol. 2012 Oct;34(5):768-78. doi:
10.3109/08923973.2012.654494. Epub 2012 Feb 3.
Emodin inhibits invasion and migration of prostate and lung cancer cells by
downregulating the expression of chemokine receptor CXCR4.
Ok S(1), Kim SM, Kim C, Nam D, Shim BS, Kim SH, Ahn KS, Choi SH, Ahn KS.
(1)College of Oriental Medicine and Institute of Oriental Medicine, Kyung Hee
University, Seoul, Republic of Korea.
Comment in
Immunopharmacol Immunotoxicol. 2013 Apr;35(2):307.
Emodin (ED), an anthraquinone derivative, has been found to inhibit
proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and
enhance chemotherapy. However, the detailed mechanism of ED related to the
regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects
cellular migration and invasion in prostate and lung cancer cells are not fully
understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in
promoting invasion and metastasis in tumors. Thus, novel agents that can
downregulate CXCR4 expression have therapeutic potential in repressing cancer
metastasis. Among ED and its derivatives, it is found that ED downregulated the
expression of both CXCR4 and HER2 without affecting cell viability in tumor
cells. The suppression of CXCR4 expression by ED was found to correlate with the
inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells.
Besides, neither proteasome inhibition nor lysosomal stabilization had any effect
on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms
unveiled that the downregulation of CXCR4 was at the transcriptional level, as
indicated by downregulation of mRNA expression and suppression of NF-κB
activation. Overall, our findings suggest that ED is a novel blocker of CXCR4
expression and, thus, has enormous potential as a powerful therapeutic agent for
metastatic cancer.
 

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