tretinoin and 1-2-distearoyllecithin

All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular therapeutic effect on lung cancer. The objective was to find whether it could enhance ATRA receptor, RAR-β expression in lung cells as it was lost in majority of cancers including lung cancer.. The study was made in an experimental C57BL/6 mice model developed by tail vein injection of B16F10 cells and in A549 human lung cancer cells. The RAR-β protein expression was studied by Immunohistochemistry/Immunocytochemistry and the mRNA expression was studied by RT-PCR and qPCR methods.. Both free and lipo-ATRA treatments showed an enhancement of RAR-β protein and gene expressions, indicating its induction on RAR β. However, lipo-ATRA treatment has shown significant induction when compared with free ATRA treatment.. Our results implies that the DSPC lipo-ATRA treatment might have accumulated more ATRA in to the target cells which might have resulted in the induction of its receptor RAR-β expression in a hypothesis of ligand induced receptor expression.

Topics: A549 Cells; Animals; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Phosphatidylcholines; Receptors, Retinoic Acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tretinoin

The all trans retinoic acid (ATRA) is found to have a promising regulatory effect on immune system and inflammatory responses in experimental research. The purpose of this study was to investigate whether this therapeutic efficiency of ATRA could be enhanced by encapsulating into a liposome formulation composed of Distearoyl-L-phosphatidylcholine (DSPC) and cholesterol utilizing a well-established mice model. The humoral antibody titer (HA), delayed-type hypersensitivity (DTH), bone marrow cellularity, hematology, and levels of α- esterase-positive cells, were taken as parameters to assess the level of immunomodulation in the sheep red blood cells (SRBC) immunized and challenged BALB/c mice. The anti-inflammatory effect of encapsulated ATRA was evaluated by the size changes in the induced inflammation edema in the mice paw as well as its histopathology. The results showed a significant immunostimulatory effect for both the free and encapsulated ATRA as indicated by the increase in the levels of total leukocyte, bone marrow and α-esterase positive cells and decreased Hb level respectively. We have also observed an enhanced specific antibody hemagglutinin titre value and the DTH response developed in response to SRBC challenge in these treatments. Both the immunostimulatory as well as inflammation reducing property were significantly higher in encapsulated ATRA treated group of mice over that of in free ATRA treated group of mice. Based on these results, we conclude that the encapsulated ATRA has a higher potency over free ATRA in its immunomodulatory activity and also has a significant impact on reducing inflammation in BALB/c mice model.

Topics: Animals; Bone Marrow; Cholesterol; Disease Models, Animal; Edema; Esterases; Immunomodulation; Inflammation; Leukocytes; Liposomes; Male; Mice; Mice, Inbred BALB C; Phosphatidylcholines; Sheep; Tretinoin

The purpose of this study was to investigate whether all trans retinoic acid (ATRA) incorporated in liposome composed of distearoylphosphatidylcholine (DSPC/cholesterol) could inhibit the metastatic lung cancer in mice more efficiently than free ATRA. Metastatic lung cancer model was developed by intravenous injection of B16F10 cells and it is also referred as melanoma model. In this present study, C57BL/6 mice were divided into several groups as per experimental design and the free ATRA and liposome encapsulated ATRA were given for 21 days at a dose of 0.60 mg/kg body weight/day after cell line implantation. After 21 days, mice were sacrificed at different time interval for ATRA level analysis in serum and lung tissue by HPLC method and the remaining mice were kept for anticancer study. The ATRA level increased significantly in serum and lung tissue in liposome encapsulated ATRA treated mice. In cancer bearing mice, tumor nodule formation decreased and life span increased after receiving liposome encapsulated ATRA treatment than free ATRA treated mice. This result implies that the liposome encapsulated ATRA has maintained more ATRA concentration in lung tissue and showed more inhibition on the lung tumor nodule formation. The results indicate a possible use of liposome encapsulated ATRA in prevention of lung metastasis.

Topics: Animals; Antineoplastic Agents; Liposomes; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Phosphatidylcholines; Tretinoin