The integrative updates are to be viewed as a kind of easy to digest Integrative cancer knowledge stream that is useful clinically. Physicians of all the professions need to be up-to-date on ways to support cancer patients. Enjoy.

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Date: Wed, 15 Apr 2009 13:07:29 -0700

Subject: Re: Plain Language version of todays
Integrative cancer update



Thanks Dr. Ervolino.

Question for you though, what about an I3C DIM
combination as a BrCA prevention?

Any thoughts you can share?

Much obliged,
Eden

Eden,
See below. I believe that adding DIM would not hurt, but
would not improve the response because in the article below
it appears that the desired effect comes from the of I3C to
metabolize into DIM and combine with Genistein to encourage
expression of BRACA1 and BRACA2. I would add genistein to
I3C instead.

British Journal of Cancer (2006)
94, 407–426. doi:10.1038/sj.bjc.6602935 www.bjcancer.com Published online 24 January 2006

BRCA1 and BRCA2 as molecular targets for
phytochemicals indole-3-carbinol and genistein in breast and
prostate cancer cells
S Fan1, Q Meng1, K Auborn2, T Carter2 and E M Rosen11Department
of Oncology, Lombardi Comprehensive Cancer Center,
Georgetown University, 3970 Reservoir Road, NW, Washington, DC
20057-1469, USA2Department of Otolaryngology, North Shore-Long Island Jewish Research Institute, BoasMarks Biomedical Science Research Center, 350 Community
Drive, Manhasset, New York 11030, USACorrespondence: Dr EM Rosen, E-mail: emr36@georgetown.eduRevised 30 November 2005; Accepted
30 November 2005; Published online 24 January 2006.

Abstract
Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals

derived from cruciferous vegetables and soy, respectively, with potential cancer

prevention activity for hormone-responsive tumours (e.g., breast and

prostate cancers). Previously, we showed that I3C induces BRCA1

expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen

receptor (ER-) activity in human breast cancer cells. We now report that

both I3C and genistein induce the expression of both breast cancer

susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and

prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent

fashion. Induction of the BRCA genes occurred at low doses of I3C

(20 M) and genistein (0.5–1.0 M), suggesting potential relevance to cancer prevention.

A combination of I3C and genistein gave greater than expected induction of

BRCA expression. Studies using small interfering RNAs (siRNAs)

and BRCA expression vectors suggest that the phytochemical induction

of BRCA2 is due, in part, to BRCA1. Functional studies suggest that

I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2.

Inhibition of E2-stimulated ER- activity by I3C and genistein was dependent upon

BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C

and genistein was partially reversed by BRCA1-siRNA. Finally,

we provide evidence suggesting that the phytochemical induction of

BRCA1 expression is due, in part, to endoplasmic reticulum stress

response signalling. These findings suggest that the BRCA genes are

molecular targets for some of the activities of I3C and genistein.

Yours in Health,

Dr Frank Ervolino

www.drervolino.com