Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB in breast cancer cel

Rich66 · 11-01-2009, 01:31 AM

Original curcumin post/discussion by Lani: http://her2support.org/vbulletin/sho...light=Curcumin

Thread by Tom:http://her2support.org/vbulletin/sho...light=Curcumin

HUGE compilation by Marge, a curcumin evangelist:
http://margaret.healthblogs.org/life...y-of-curcumin/

Marge's warning/side effects page: avoid if gall bladder issues, taking blood thinners, stomach ulcers. See smoker issue below
Others say Curcumin treats gallstones. maybe depends on which type of gallstone (bile or cholesterol)
pubmed says:

Asia Pac J Clin Nutr. 2002;11(4):314-8.
Effect of different curcumin dosages on human gall bladder.

Rasyid A, Rahman AR, Jaalam K, Lelo A.
School of Medicine, University of North Sumatera, Medan, Indonesia. rasyid_1506@yahoo.com
Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.

PMID: 12495265 [PubMed - indexed for MEDLINE]

Ok...back to cancer related...

Dr. Aagarwal's extensive website: www.curcuminresearch.org

Interview with Dr. Aagarwal: http://www.naturalmedicinejournal.co...J_DEC09_RI.pdf

Curcumin discussion thread in Prostate Cancer forum

Breast J. 2009 May-Jun;15(3):223-9.
Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB in breast cancer cells and potentiates the growth inhibitory effect of paclitaxel in a breast cancer nude mice model.

FULL TEXT(free)

Kang HJ, Lee SH, Price JE, Kim LS.
Division of Breast & Endocrine Surgery, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Dongan-Gu, Anyang, Korea.
Most anticancer agents activate nuclear factor kappa B (NF-kappaB), which can mediate cell survival, proliferation, and metastasis. Curcumin has been shown to inhibit the growth of various cancer cells, without toxicity to normal cells. The antitumor effects of curcumin could be due in part to the inactivation of NF-kappaB. We hypothesize that blocking NF-kappaB activity may augment paclitaxel cancer chemotherapy. In this study, we investigated whether the inactivation of NF-kappaB by curcumin would enhance the efficacy of paclitaxel for inhibiting breast cancer growth in vitro and in vivo. We confirmed that curcumin inhibited paclitaxel-induced activation of NF-kappaB and potentiated the growth inhibitory effect of paclitaxel in MDA-MB-231 breast cancer cells. The combination of curcumin with paclitaxel elicited significantly greater inhibition of cell growth and more apoptosis, compared with either agent alone. In an experimental breast cancer murine model using MDA-MB-231 cells, combination therapy with paclitaxel and curcumin significantly reduced tumor size and decreased tumor cell proliferation, increased apoptosis, and decreased the expression of matrix metalloprotease 9 compared with either agent alone. These results clearly suggest that a curcumin-paclitaxel combination could be a novel strategy for the treatment of breast cancer.

PMID: 19645775 [PubMed - indexed for MEDLINE]

[The below refers to lung cancer, not sure if related to other cancer mets. (Tom's friend had lung met reduction) ]

1: Carcinogenesis. 2009 Apr 9.: Lung tumor promotion by curcumin.
: http://carcin.oxfordjournals.org/cgi...ract/30/6/1016; To whom correspondence should be addressed. Department of Cancer Biology, 1 Medical Center Boulevard, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. Tel: +1 336 716 0795; Fax: +1 336 716 0255; Email: msmiller@wfubmc.edu

Dance-Barnes ST, Kock ND, Moore JE, Lin EY, Mosley LJ, D'Agostino RB Jr, McCoy TP, Townsend AJ, Miller MS.
Department of Cancer Biology.
Curcumin exhibits anti-inflammatory and anti-tumor activity and is being tested in clinical trials as a chemopreventive agent for colon cancer. Curcumin's chemopreventive activity was tested in a transgenic mouse model of lung cancer that expresses the human Ki-ras(G12C) allele in a doxycycline (DOX) inducible and lung-specific manner. The effects of curcumin were compared to the lung tumor promoter, butylated hydroxytoluene (BHT), and the lung cancer chemopreventive agent, sulindac. Treatment of DOX-induced mice with dietary curcumin increased tumor multiplicity (36.3+/-0.9 vs. 24.3+/-0.2) and progression to later stage lesions, results which were similar to animals that were co-treated with DOX/BHT. Microscopic examination showed that the percentage of lung lesions that were adenomas and adenocarcinomas increased to 66% in DOX/BHT, 66% in DOX/curcumin, and 49% in DOX/BHT/curcumin treated groups relative to DOX only treated mice (19%). Immunohistochemical analysis also showed increased evidence of inflammation in DOX/BHT, DOX/curcumin, and DOX/BHT/curcumin mice relative to DOX only treated mice. In contrast, co-treatment of DOX/BHT mice with 80 ppm of sulindac inhibited the progression of lung lesions and reduced the inflammation. Lung tissue from DOX/curcumin treated mice demonstrated a significant increase (33%; p = 0.01) in oxidative damage, as assessed by the levels of carbonyl protein formation, relative to DOX-treated control mice after one week on the curcumin diet. These results suggest that curcumin may exhibit organ-specific effects to enhance reactive oxygen species formation in the damaged lung epithelium of smokers and ex-smokers. Ongoing clinical trials thus may need to exclude smokers and ex-smokers in chemopreventive trials of curcumin.

"The Dark side of Curcumin" PDF (oral availability, dose dependent effects etc)

1: Ann N Y Acad Sci. 2009 Feb;1155:278-83. Links: Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer.

Labbozzetta M, Notarbartolo M, Poma P, Maurici A, Inguglia L, Marchetti P, Rizzi M, Baruchello R, Simoni D, D'Alessandro N.
Dipartimento di Scienze Farmacologiche Pietro Benigno, UniversitÃ* di Palermo, Palermo, Italy.
We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.

Some say oral Curcumin absorption is too low for cancer benefit and a different delivery approach is necessary.
Others say:

Mol Nutr Food Res. 2008 Sep;52(9):1010-30.
Multi-targeted therapy by curcumin: how spicy is it?

Goel A, Jhurani S, Aggarwal BB.
Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
Comment in:

Mol Nutr Food Res. 2009 Feb;53(2):308.

Although traditional medicines have been used for thousands of years, for most such medicines neither the active component nor their molecular targets have been very well identified. Curcumin, a yellow component of turmeric or curry powder, however, is an exception. Although inhibitors of cyclooxygenase-2, HER2, tumor necrosis factor, EGFR, Bcr-abl, proteosome, and vascular endothelial cell growth factor have been approved for human use by the United States Food and Drug Administration (FDA), curcumin as a single agent can down-regulate all these targets. Curcumin can also activate apoptosis, down-regulate cell survival gene products, and up-regulate p53, p21, and p27. Although curcumin is poorly absorbed after ingestion, multiple studies have suggested that even low levels of physiologically achievable concentrations of curcumin may be sufficient for its chemopreventive and chemotherapeutic activity. Thus, curcumin regulates multiple targets (multitargeted therapy), which is needed for treatment of most diseases, and it is inexpensive and has been found to be safe in human clinical trials. The present article reviews the key molecular mechanisms of curcumin action and compares this to some of the single-targeted therapies currently available for human cancer.

PMID: 18384098 [PubMed - indexed for MEDLINE]

Int J Cancer. 2009 Jul 1;125(1):1-8.
Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice.

Narayanan NK, Nargi D, Randolph C, Narayanan BA.
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Narayanan.Narayanan@nyumc.org
Comment in:

Int J Cancer. 2009 Oct 15;125(8):1992-3.

Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clinical use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examined the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC analysis of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Molecular targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.

PMID: 19326431 [PubMed - indexed for MEDLINE]

Ai Zheng. 2010 Jan;29(1):9-14.
The aromatase inhibitor letrozole combined with curcumin in the inhibition of xenografted endometrial carcinoma growth.

Liang YJ, Zhang HM, Wu YZ, Hao Q, Wang JD, Hu YL.
Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Medicine,Nanjing, Jiangsu 210002, P. R. China. yuanjiao1965@126.com.
Background and Objective: Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma. Tumor inhibition to a certain extent has been demonstrated, however, the therapeutic effects need improvement. Curcumin is reported to have antitumor capabilities and can enhance the sensitivity of tumor cells to anticancer agents. The present study promoted the inhibitory effect on implanted endometrial tumor growth by combining letrozole and curcumin. Methods: Endometrial carcinoma was implanted into nude mice. Tumor-laden mice were treated with the aromatase inhibitor letrozole (Let), curcumin (Cur), or both. The tumor growth was monitored. Tumor cell apoptosis was detected in both the control and treated groups. The expression of bcl-2 mRNA and Bcl-2 protein was detected with reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Results: A total of 50 mice successfully received implants of endometrial tumors. Treatment with letrozole markedly inhibited tumor growth, and the inhibitory effect was enhanced by the combination of letrozole and curcumin. The inhibitory rates in the Let(1), Let(10), Cur, and Let+Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of Bcl-2 in tumor cells at the mRNA and protein levels. The rates of apoptosis in the control group and the above-mentioned groups were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cell apoptosis was observed in mice treated with either letrozole or curcumin; however, the combination of letrozole and curcumin enhanced the inhibition rate in tumor growth. Conclusions: Treatment with either letrozole or curcumin could inhibit xenografted endometrial tumor growth by inducing apoptosis in tumor cells. The combination of letrozole and curcumin enhanced the inhibitory effect.

PMID: 20038303 [PubMed - in process]