Systemic and local injections of lupeol inhibit tumor growth in a melanoma-bearing mouse model.

Melanoma is the most aggressive type of skin cancer and it is procured from activated or genetically altered epidermal melanocytes. In the present study, the tumor-suppressive effects of systemic and local injections of lupeol, a triterpene extracted from Indian lettuce (Lactuca indica), in a melanoma-bearing mouse model were evaluated. Mice were injected once with lupeol or olive oil (solvent control) subcutaneously into the skin of the back or into the tumor tissue. Seven days after the injection, the tumor growth rates were calculated and the tumor tissues were collected. Immunohistochemical staining for Ki-67 and proliferating cell nuclear antigen (PCNA) were performed. The tumor growth rates in the lupeol-injected group were significantly decreased compared to those observed in the non-treated (NT) and solvent control groups. Lupeol also significantly decreased the areas positively stained for Ki-67 and PCNA in the tumor tissues compared to those in the NT and solvent control groups. The results of the present study demonstrated that systemic and local injections of lupeol suppress tumor growth and induce cell cycle arrest in a melanoma-bearing mouse model. These data suggest that lupeol may be effective as a novel therapeutic option for melanoma patients.

Melanoma cell differentiation induced by lupeol separates into two stages: morphological and functional changes.

Electron microscopic observation revealed that lupeol induced melanosome maturation in B16 2F2 mouse melanoma cells and we therefore studied the effects of lupeol on the intracellular events responsible for melanosome transport. Incubation with lupeol for 8 h attenuated the actin stress fiber assembly in B16 2F2 mouse melanoma cells, resulting in dendritic formation in the cells. Longer exposure to lupeol (48 h) increased the expression of tyrosinase, MITF (a specific transcription factor for tyrosinase), Rab27a, and myosin-Va, which are required for melanosome transport.

Canine bone marrow cells differentiate into hepatocyte-like cells and placental hydrolysate is a potential inducer.

Hepatocyte growth factor (HGF) can stimulate human and rat bone marrow (BM) cells to differentiate into hepatocytes. A human placental hydrolysate (hPH) stimulates proliferation of hepatocytes, but its role as a potential inducer of BM cells to form hepatocytes is unclear. To determine if canine BM cells stimulated with HGF or hPH differentiate into hepatocyte-like cells, BM cells were cultured with HGF or hPH. The cultured cells underwent morphological examination, expression of albumin and cytokeratin 18 (CK18), hepatic function tests including uptake of low-density lipoprotein (LDL) and cytochrome P (CYP) 450 activity. Albumin mRNA and protein expression of albumin and CK18 proteins were detected in cultures with HGF and hPH. Furthermore, these cells demonstrated LDL uptake and CYP450 activity. These results indicate that canine BM cells can differentiate into hepatocyte-like cells when stimulated by both HGF and that hPH may be an effective inducer of hepatic differentiation.