Curcumin analog DM-1 in monotherapy or combinatory treatment with dacarbazine as a...
| Full text | |
| Author(s): |
de Souza, Nayane
[1]
;
de Oliveira, Erica Aparecida
[1]
;
Faiao-Flores, Fernanda
[1]
;
Pimenta, Luciana A.
[2]
;
Quincoces, Jose A. P.
[3]
;
Sampaio, Sandra C.
[2]
;
Maria-Engler, Silvya S.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Sch Pharmaceut Sci, Clin Chem & Toxicol Dept, Skin Biol Grp, FCF USP, Sao Paulo - Brazil
[2] Butantan Inst, Pathophysiol Lab, Sao Paulo - Brazil
[3] Anhanguera Univ Sao Paulo, UNIAN, Lab Organ Synth, Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 20, n. 9, p. 1038-1050, 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Background: Melanoma is the most aggressive skin cancer, and BRAF (V600E) is the most frequent mutation that led to the development of BRAF inhibitors (BRAFi). However, patients treated with BRAFi usually present recidivism after 6-9 months. Curcumin is a turmeric substance, and it has been deeply investigated due to its anti-inflammatory and antitumoral effects. Still the low bioavailability and biodisponibility encouraged the investigation of different analogs. DM-1 is a curcumin analog and has shown an antitumoral impact in previous studies. Methods: Evaluated DM-1 stability and cytotoxic effects for BRAFi-sensitive and resistant melanomas, as well as the role in the metalloproteinases modulation. Results: DM-1 showed growth inhibitory potential for melanoma cells, demonstrated by reduction colony formation, migration and endothelial tube formation, and cell cycle arrest. Subtoxic doses were able to down-regulate important Metalloproteinases (MMPs I related to invasiveness, such as MMP-1, -2 and -9. Negative modulations of TEMP-2 and MMP-14 reduced MMP-2 and -9 activity; however, the reverse effect is seen when increased TIMP-2 and MMP-14 resulted in raised MMP-2. Conclusion: These findings provide essential details into the functional role of DM-1 in melanomas, encouraging further studies in the development of combinatorial treatments for melanomas. (AU) | |
| FAPESP's process: | 16/16554-3 - Emerging genes in melanoma progression and chemoresistance |
| Grantee: | Érica Aparecida de Oliveira |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| FAPESP's process: | 13/05172-4 - Impact of epithelial-mesenchymal transition proteins ín vemurafenib chemoresistant melanoma |
| Grantee: | Fernanda Faião Flores |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| FAPESP's process: | 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets |
| Grantee: | Silvya Stuchi Maria-Engler |
| Support type: | Research Projects - Thematic Grants |