In vivo method for treating, inhibiting, and/or prophylaxis of cancer, such as pancreatic cancer
Inventors
Dhar, Animesh • Gutheil, William G.
Assignees
University of Kansas • US Department of Veterans Affairs • University of Missouri Columbia
Publication Number
US-9889105-B2
Publication Date
2018-02-13
Expiration Date
2031-10-07
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Abstract
An in vivo method of inhibiting tumor growth, specifically pancreatic cancer, includes administering to a subject in need thereof an effective amount of a compound, composition, and/or a pharmaceutical formulation including crocetinic acid.
Core Innovation
The invention provides an in vivo method for treating, inhibiting, and/or prophylaxis of cancer, specifically pancreatic cancer, by administering an effective amount of a compound, composition, or pharmaceutical formulation comprising crocetinic acid to a subject in need thereof. The invention involves purifying or fractionating crude crocetin to obtain a novel crocetin compound, crocetinic acid, which is about 50-times more potent than crude crocetin and has low toxicity. This compound is utilized to inhibit tumor growth, proliferation of cancer cells, stimulate apoptosis, and impair the self-renewal of cancer stem cells both in vitro and in vivo.
The problem addressed by the invention stems from the significant prevalence and mortality of pancreatic cancer, which ranks as the fourth leading cause of cancer deaths worldwide with no significant effective treatment currently available. Existing studies have shown that crude crocetin and saffron extracts possess antitumor properties but their potency and mechanisms were not fully characterized or optimized. The present invention solves this by isolating a purified and more potent form of crocetin, crocetinic acid, which exhibits enhanced anti-proliferative and pro-apoptotic effects on pancreatic cancer cells and inhibits tumor progression in animal models by targeting cancer stem cells and downregulating key sonic hedgehog signaling pathways involved in tumorigenesis.
Claims Coverage
There is one independent claim focusing on an in vivo method targeting cancer stem cells using crocetinic acid with specified dosage and effect on sonic hedgehog signaling.
In vivo impairment of cancer stem cell self-renewal using crocetinic acid
A method comprising providing a predetermined amount of cancer stem cells and subjecting them to an effective amount of crocetinic acid in an amount between and including 0.5 mg/kg and 4 mg/kg body weight to inhibit the expression of Sonic Hedgehog signaling in the cancer stem cells.
The independent claim covers the novel in vivo method of administering crocetinic acid at specific dosages to impair self-renewal of cancer stem cells by inhibiting Sonic Hedgehog signaling, specifically including pancreatic stem cells as recited in the dependent claim.
Stated Advantages
Crocetinic acid is approximately 50 times more potent than crude crocetin in inhibiting proliferation and stimulating apoptosis of pancreatic cancer cells.
It exhibits low toxicity making it suitable for therapeutic use.
The compound effectively inhibits tumor growth in vivo in pancreatic cancer xenograft models.
Crocetinic acid specifically targets cancer stem cells by impairing self-renewal through downregulation of the sonic hedgehog signaling pathway, contributing to tumorigenesis inhibition.
It significantly reduces EGFR and Akt signaling pathways, contributing to its anti-proliferative effects.
Documented Applications
In vivo treatment, inhibition, and prevention of pancreatic cancer by administering crocetinic acid to inhibit tumor growth.
Use of crocetinic acid to inhibit proliferation and stimulate apoptosis of pancreatic cancer cells in vitro and in vivo.
Method of impairing or preventing self-renewal of pancreatic cancer stem cells using crocetinic acid.
Use of crocetinic acid in combination with other anticancer agents for therapy, treatment, and/or prevention of pancreatic cancer.
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