Materials and methods for treatment of cancer and identification of anti-cancer compounds
The subject invention pertains to the treatment of tumors and cancerous tissues and the prevention of tumorigenesis and malignant transformation through the modulation of JAK/STAT3 intracellular signaling. The subject invention concerns pharmaceutical compositions containing cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof. Another aspect of the invention concerns methods of inhibiting the growth of a tumor by administering a cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, to a patient, wherein the tumor is characterized by the constitutive activation of the JAK/STAT3 intracellular signaling pathway. The present invention further pertains to methods of moderating the JAK and/or STAT3 signaling pathways in vitro or in vivo using cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof. Another aspect of the present invention concerns a method for screening candidate compounds for JAK and/or STAT3 inhibition and anti-tumor activity.
1. A method for treating non-small cell lung cancer comprising administering cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, or a composition comprising cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, to a patient in need of such treatment.
2. The method according to claim 1 , wherein the analog is selected from the group consisting of cucurbitacin A, cucurbitacin B, cucurbitacin D, cucurbitacin E, cucurbitacin Q, and tetrahydro-cucurbitacin I.
3. The method according to claim 1 , wherein the analog inhibits STAT3 signaling pathway, but does not inhibit JAK2 signaling pathway.
4. The method according to claim 1 , wherein the cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, inhibits STAT3 signaling pathway.
5. The method according to claim 1 , wherein the cancer is characterized by abnormal STAT3 pathway activity.
6. The method according to claim 1 , wherein the cancer is characterized by abnormal JAK2 pathway activity and abnormal STAT3 pathway activity.
7. The method according to claim 1 , wherein cucurbitacin I, or a pharmaceutically acceptable salt thereof, is administered to the patient.
8. The method according to claim 1 , wherein route of said administration is selected from the group consisting of intravenous, intramuscular, oral, and intra-nasal.
9. The method according to claim 1 , wherein the patient is suffering from a tumor and the cucurbitacin I, or the pharmaceutically acceptable salt or analog thereof, inhibits growth of the tumor.
10. The method according to claim 1 , wherein the analog is cucurbitacin Q having the chemical structure:
11. The method according to claim 1 , wherein the cancer is characterized by constitutive activity of STAT3 signaling pathway.
12. The method according to claim 1 , wherein the cancer is characterized by constitutive activation of both JAK2 and STAT3 signaling pathways.
13. The method according to claim 1 , wherein the non-small cell lung cancer is an adenocarcinoma.
14. The method according to claim 1 , wherein cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, or a composition comprising cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, is administered in conjunction with chemotherapy to treat the cancer.
15. The method according to claim 1 , wherein the analog is cucurbitacin A.
16. The method according to claim 1 , wherein the analog is cucurbitacin B.
17. The method according to claim 1 , wherein the analog is cucurbitacin D.
18. The method according to claim 1 , wherein the analog is cucurbitacin E.
19. The method according to claim 1 , wherein the analog is tetrahydro-cucurbitacin I.