Novel Crocetin Compound For Prevention and Therapy of Pancreatic Cancer
Patent Number: WO2012060854
Executive Summary:
General Description:
Saffron, a spice and a food colorant present in the dry stigmas of the plant Crocus sativus L., was used as an herbal remedy for cancer by several ancient cultures. Crocetin, an important carotenoid constituent of saffron, has been identified as the main driver of saffron's anti-tumor activity. An extracted form of purified crocetinic acid from saffron has demonstrated significant anti-tumor activity against pancreatic cancer cells in a mouse model with low toxicity.
Scientific Progress:
Research by Dr. Dhar and his collaborators indicates that crocetin inhibits DNA synthesis and RNA polymerase II activity, that in turn, inhibits proliferation by impairing EGFR, phospho Cdc-2, Cdc25c, cyclin B1 and increases apoptosis by enhancing the ratio of Bax/Bcl-2 that ultimately inhibits tumor formation. Crocetin also inhibits oxidant injury due to lipid peroxidation and these antioxidant effects could be responsible for inhibition of tumor formation.
The team also purified crocetinic acid from crocetin. Crocetinic acid inhibits proliferation of pancreatic cancer cell lines and induces apoptosis. Crocetinic acid targets cancer stem cells (CSC), thereby inhibiting pancreatic tumorigenesis. The compound was validated in vitro and in a xenograft mouse model.
Future Directions:
Strengths:
Natural compound, so low toxicity expected
Weaknesses:
Patentability of the parent compound
Patent Status:
Publication PMID: 19208826, 26317547
Publications:
Dhar A, Mehta S, Dhar G, Dhar K, Banerjee S, Van Veldhuizen P, Campbell DR, Banerjee SK. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009 Feb;8(2):315-23. doi: 10.1158/1535-7163.MCT-08-0762. Epub 2009 Feb 10. Erratum in: Mol Cancer Ther. 2009 Mar;8(3):711.
Rangarajan P, Subramaniam D, Paul S, Kwatra D, Palaniyandi K, Islam S, Harihar S, Ramalingam S, Gutheil W, Putty S, Pradhan R, Padhye S, Welch DR, Anant S, Dhar A. Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells. Oncotarget. 2015 Sep 29;6(29):27661-73. doi: 10.18632/oncotarget.4871.
Inventor Bio: Animesh Dhar
http://www.kumc.edu/school-of-medicine/cancer-biology/faculty/animesh-dhar-phd.html
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Application pending
- Patent Link: https://kuic.ku.edu/available-technology/novel-crocetin-compound-prevention-and-therapy-pancreatic-cancer
- Research Institute: University of Kansas
- Disease Focus: Pancreatic Cancer
- Basis of Invention: Crocetin is a carotenoid compound derived from saffron
- How it works: Crocetin inhibits pancreatic cancer cell proliferation and induces apoptosis
- Lead Challenge Inventor: Animesh Dhar
- Inventors: William Gutheil, Animesh Dhar
- Development Stage: Preclinical
- Novelty: Novel use of crocetin for cancer prevention and therapy
- Clinical Applications: In addition to pancreatic cancer, crocetin has demonstrated anti-oncolytic activity in breast, lung, cervical, leukemia, colorectal, liver, and skin cancers. It can be used both as an adjuvant therapeutic to conventional chemotherapeutic agents and alone as a chemopreventive agent
General Description:
Saffron, a spice and a food colorant present in the dry stigmas of the plant Crocus sativus L., was used as an herbal remedy for cancer by several ancient cultures. Crocetin, an important carotenoid constituent of saffron, has been identified as the main driver of saffron's anti-tumor activity. An extracted form of purified crocetinic acid from saffron has demonstrated significant anti-tumor activity against pancreatic cancer cells in a mouse model with low toxicity.
Scientific Progress:
Research by Dr. Dhar and his collaborators indicates that crocetin inhibits DNA synthesis and RNA polymerase II activity, that in turn, inhibits proliferation by impairing EGFR, phospho Cdc-2, Cdc25c, cyclin B1 and increases apoptosis by enhancing the ratio of Bax/Bcl-2 that ultimately inhibits tumor formation. Crocetin also inhibits oxidant injury due to lipid peroxidation and these antioxidant effects could be responsible for inhibition of tumor formation.
The team also purified crocetinic acid from crocetin. Crocetinic acid inhibits proliferation of pancreatic cancer cell lines and induces apoptosis. Crocetinic acid targets cancer stem cells (CSC), thereby inhibiting pancreatic tumorigenesis. The compound was validated in vitro and in a xenograft mouse model.
Future Directions:
- Development of analogs
Strengths:
Natural compound, so low toxicity expected
Weaknesses:
Patentability of the parent compound
Patent Status:
- Priority date: 2010-11-02
- Application date: 2012-02-09
Publication PMID: 19208826, 26317547
Publications:
Dhar A, Mehta S, Dhar G, Dhar K, Banerjee S, Van Veldhuizen P, Campbell DR, Banerjee SK. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009 Feb;8(2):315-23. doi: 10.1158/1535-7163.MCT-08-0762. Epub 2009 Feb 10. Erratum in: Mol Cancer Ther. 2009 Mar;8(3):711.
Rangarajan P, Subramaniam D, Paul S, Kwatra D, Palaniyandi K, Islam S, Harihar S, Ramalingam S, Gutheil W, Putty S, Pradhan R, Padhye S, Welch DR, Anant S, Dhar A. Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells. Oncotarget. 2015 Sep 29;6(29):27661-73. doi: 10.18632/oncotarget.4871.
Inventor Bio: Animesh Dhar
http://www.kumc.edu/school-of-medicine/cancer-biology/faculty/animesh-dhar-phd.html