In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers

EBioMedicine
Qing-Bin LuJenny Warrington

Abstract

Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers.

References

Dec 7, 1995·Nature·D M Reese
May 2, 1996·The New England Journal of Medicine·G S OmennS Hammar
Jul 29, 1998·Chemico-biological Interactions·P CalvertP J O'Dwyer
Mar 7, 2006·Critical Reviews in Clinical Laboratory Sciences·José M EstrelaElena Obrador
May 27, 2006·Science·Harold Varmus
Oct 23, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Charity Mosley-ForemanHongtao Yu
Oct 5, 2010·Journal of the American Chemical Society·Chun-Rong Wang, Qing-Bin Lu
Mar 26, 2011·Science·Bruce Alberts
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jenny NguyenQing-Bin Lu
Jun 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ting LuoQing-Bin Lu
Jun 15, 2013·Oxidative Medicine and Cellular Longevity·Nicola TraversoCinzia Domenicotti

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM05757

Methods Mentioned

BETA
flow cytometry
xenograft
xenografts
surgical resection

Software Mentioned

FlowJo
Image J

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

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