Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Gema Perez-ChaconJuan M Zapata

Abstract

Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival. Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice. I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice. I3C in combination with ...Continue Reading

References

Oct 19, 1995·The New England Journal of Medicine·C Rozman, E Montserrat
Aug 6, 2000·Gynecologic Oncology·M C BellJ M Mathis
May 25, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mark J AndertonDonald E Mager
Jun 15, 2004·Journal of Voice : Official Journal of the Voice Foundation·Clark A Rosen, Paul C Bryson
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mark J AndertonMarion L Williams
Feb 25, 2005·The New England Journal of Medicine·Nicholas ChiorazziManlio Ferrarini
Aug 6, 2005·Cell Cycle·Bharat B Aggarwal, Haruyo Ichikawa
Aug 17, 2005·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Gregory A ReedAryeh Hurwitz
May 10, 2006·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·R NaikJ M Monaghan
Dec 14, 2006·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Gregory A ReedAryeh Hurwitz
Mar 4, 2008·Cancer Letters·Jing-Ru WengChing-Shih Chen
Apr 30, 2009·Cancer·Apostolia-Maria Tsimberidou, Michael J Keating
Oct 6, 2010·The Journal of Biological Chemistry·Weihong WenZigang Dong
May 31, 2013·American Journal of Hematology·Michael Hallek
Jun 22, 2013·Leukemia Research·Joshua Lukenbill, Matt Kalaycio
Jul 9, 2013·Seminars in Cancer Biology·Federico Caligaris-CappioCristina Scielzo
Aug 31, 2013·Annual Review of Pathology·Suping Zhang, Thomas J Kipps
Dec 11, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elisa ten Hacken, Jan A Burger
Sep 3, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gema Perez-ChaconJuan M Zapata
Apr 1, 2015·Journal of Biomaterials Applications·Dena TilaSaeed Ghanbarzadeh

❮ Previous
Next ❯

Citations

Nov 18, 2018·Mini Reviews in Medicinal Chemistry·Mojgan Noroozi KarimabadGholamhossein Hassanshahi
Aug 17, 2017·Journal of Receptor and Signal Transduction Research·Saeed MohammadiYaghoub Yazdani
Jul 2, 2020·Seminars in Cancer Biology·Elina KhatoonAjaikumar B Kunnumakkara
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Coralia CotoraciAnca Hermenean

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis