Treatment of Metastatic Melanoma B16F10 by the Flavonoids Tangeretin, Rutin, and Diosmin

Abstract

Melanoma is one of the most frequently metastasizing malignant neoplasias. This study examines an experimental model of pulmonary metastasis and the B16F10 cell subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered to be necessary because it is used as a vehicle for administering the flavonoids. Lentini's model, which complements the macroscopic evaluation of nodule numbers by using a stereoscopic microscope and image analysis at the microscopic level, was used. The greatest reduction in the number of metastatic nodules (52%) was obtained with diosmin; similarly, the percentages of implantation, growth index, and invasion index (79.40, 67.44, and 45.23%, respectively), were all compared with those of the ethanol group, considered to be an effective control group. Rutin- and tangeretin-treated groups also showed reductions of the same index compared with the ethanol group. It would seem that structural factors would better explain these results and the antimetastatic activity of each flavonoid and the respective metabolites.

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities

“…In brain tumors, tangeretin exhibited inhibitory activity on the adhesion, migration, invasion, and MMP-2/MMP-9 secretion in brain tumors that were taken as surgical samples from patients [198]. In melanoma, the invasion of B16F10 cells was inhibited by the treatment of tangeretin [199].…”

Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

“…Moreover, naringin inhibited cell migration and invasion of chondrosarcoma cells via vascular cell adhesion molecule 1 (VCAM-1) down-regulation by increasing miR-126 [186], while in bladder cancer cells it downregulated the Akt and MMP-2 pathways [187]. In an experimental model of pulmonary metastasis generated by inoculating albino Swiss mice with highly metastatic murine melanoma cells B16F10, diosmin reduced the number of metastatic nodules in the lung more effectively than tangeretin and rutin [188]. Furthermore, oral administration of naringenin or hesperitin reduced the number of lung metastases in C57BL6/N mice inoculated with B16F10 cells, and increased survival time after tumor cell inoculation [189].…”

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

“…Cucurbitacin B (cucB), a triterpenoid from Cucurbitaceae vegetables also found in bitter melon seeds, caused cell cycle arrest and apoptosis induction in human colon adenocarcinoma cancer cells [53]. Additionally, Rutin, a flavonoid present in bitter melon leaves, has been reported to display growth inhibition of leukemia and ovarian carcinoma cells, with anti-invasive effects on melanoma cells [35,[56][57][58]. Therefore, BMLE may include other bioactive compounds apart from kuguacin J, which exert anti-tumor effects, although human studies have not yet been published.…”

“…Moreover, 2 flavonoids and 4 phenolic acids, including rutin, naringin, gentistic acid, benzoic acid, ocoumaric acid, and t-cinnamic acid, are present in bitter melon leaves [35]. Rutin, a flavonoid glycoside, has been reported to successfully show growth inhibition of leukemia and ovarian carcinomas, with anti-invasive effects on melanoma [35,[56][57][58]. Triterpenoids and flavoniods included in bitter melon leaf extract (BMLE) might be promising components with critical roles against cancer cell progression, but the active compound(s) remain to be identified.…”