cholecalciferol and Lymphoma

Topics: Animals; Bone Resorption; Calcitriol; Cell Line; Cell Transformation, Neoplastic; Cholecalciferol; Culture Techniques; Gene Expression Regulation; Granulocytes; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma; Mice; Monocytes; Oncogenes; Transcription, Genetic

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Azathioprine; Chloroquine; Cholecalciferol; Chronic Disease; Erythema Nodosum; Female; Humans; Levamisole; Lung Diseases; Lung Neoplasms; Lymphoma; Penicillamine; Sarcoidosis; Syndrome; Uveitis, Anterior

Topics: Cholecalciferol; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Vitamin D Deficiency

Non-coding micro-RNA (miRNAs) regulate the protein expression responsible for cell growth and proliferation. miRNAs also play a role in a cancer cells' response to drug treatment. Knowing that leukemia and lymphoma cells show different responses to active forms of vitamin D

Topics: Cell Line; Cell Proliferation; Cholecalciferol; Humans; Leukemia; Lymphoma; MicroRNAs; Vitamin D3 24-Hydroxylase

FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo-[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone; FR901228, depsipeptide] is a novel histone deacetylase inhibitor that shows therapeutic efficacy in Phase I trials of patients with malignant lymphoma. However, its mechanism of action has not been characterized. In this study, we examined the in vitro and in vivo effects of FK228 on human lymphoma U-937 cells. FK228 very strongly inhibited the growth of U-937 cells with an IC(50) value of 5.92 nM. In a scid mouse lymphoma model, mice treated with FK228 once or twice a week survived longer than control mice, with median survival times of 30.5 (0.56 mg/kg) and 33 days (0.32 mg/kg), respectively (vs. 20 days in control mice). Remarkably, 2 out of 12 mice treated with FK228 (0.56 mg/kg once or twice a week) survived past the observation period of 60 days. The apoptotic population of U-937 cells time-dependently increased to 37.7% after 48 hr of treatment with FK228. In addition, FK228 induced G1 and G2/M arrest and the differentiation of U-937 cells to the CD11b(+)/CD14(+) phenotype. Expression of p21(WAF1/Cip1) and gelsolin mRNA increased up to 654- and 152-fold, respectively, after 24hr of treatment with FK228. FK228 caused histone acetylation in p21(WAF1/Cip1) promoter regions, including the Sp1-binding sites. In conclusion, (i) FK228 prolonged the survival time of scid mice in a lymphoma model, and (ii) the beneficial effects of FK228 on human lymphoma may be exerted through the induction of apoptosis, cell cycle arrest, and differentiation via the modulation of gene expression by histone acetylation.

Topics: Acetylation; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Apoptosis; Cell Cycle; Cell Differentiation; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Depsipeptides; Disease Models, Animal; Gelsolin; Histone Deacetylase Inhibitors; Histones; Humans; Leukemia; Lymphoma; Mice; Mice, SCID; Neoplasm Transplantation; Peptides, Cyclic; Promoter Regions, Genetic; RNA, Messenger; Tretinoin; U937 Cells; Xenograft Model Antitumor Assays

Vitamin D3 (D3) has been found to exert varied pharmacological actions including restriction of cell growth of a number of malignant cell lines in vitro and inhibition of the promotion of chemical carcinogenesis in mouse skin. In an attempt to confirm the efficacy of D3 as an antineoplastic agent, the present investigation aims at characterizing the importance of D3 in modulating hepatic drug metabolizing enzymes, namely, cytosolic glutathione S-transferase (GSHT), microsomal UDP glucuronyl transferase (UDPGT), and cytochrome P-450, which have been reported by us in recent literature as significant neoplastic markers in mice bearing Dalton's lymphoma (DL). Results show that D3 causes a 150% elevation of GSHT activity and the maintenance of normal, near-control UDPGT activity and cytochrome P-450 content, up to almost 30 days following tumor transplantation, along with bringing about a twofold increase in survival of the host mice. In conclusion, we confirm the definite and significant antitumorigenic role of D3 and its involvement with the discussed hepatic tumor markers in monitoring the processes that lead to cell survival.

Topics: Animals; Antineoplastic Agents; Cholecalciferol; Cytochrome P-450 Enzyme System; Cytosol; Glucuronosyltransferase; Glutathione Transferase; Liver; Lymphoma; Male; Mice; Microsomes, Liver; Neoplasm Transplantation; Time Factors

Annexin VIII is a calcium- and phospholipid-binding protein with anticoagulant activity. Annexin VIII mRNA was found to be specifically expressed in acute promyelocytic leukemia (APL) cells; it was not found in other types of acute myeloid leukemia (AML) nor in lymphoid malignancies. Using Northern blot analysis we investigated annexin VIII expression in 142 continuous human leukemia and lymphoma cell lines at the mRNA level. While the only APL cell line, NB-4, was indeed positive, other cell lines also displayed annexin VIII mRNA: 4/22 myeloid cell lines, 8/23 monocytic cell lines, 2/8 megakaryoblastic cell lines, 5/26 lymphoma-derived cell lines, 2/10 myeloma cell lines and 1/44 lymphoid leukemia cell lines. The strongest expression was seen in NB-4 and in the Hodgkin's disease derived cell line HDLM-2. Treatment of NB-4 cells with all-trans retinoic acid (ATRA) or the phorbol ester TPA induced terminal differentiation and down-regulated annexin VIII mRNA expression rapidly within a few hours; vitamin D3 was ineffective in this regard; the protein kinase C activator Bryostatin 1 up-regulated the expression. A panel of initially negative cell lines could not be induced by any of these biomodulators to transcribe annexin VIII. The half-life (T1/2) of annexin VIII mRNA was about 3-4 h using actinomycin D as transcription inhibitor. Treatment with ATRA or TPA prior to exposure to actinomycin shortened the T1/2 to 2 h while Bryostatin 1 extended it to 6h. As 21/141 non-APL cell lines were positive, annexin VIII cannot be used as a marker gene for APL cells; however, it might be associated with myelomonocytic or erythro-megakaryoblastic precursor cells. Annexin VIII gene expression might play a unique role in the proliferation and/or differentiation of leukemic cells and could be associated with the particular abnormal hemostasis of some leukemias.

Topics: Annexins; Blotting, Northern; Bryostatins; Cell Differentiation; Cholecalciferol; Dactinomycin; Gene Expression Regulation, Neoplastic; Half-Life; Humans; Lactones; Leukemia; Leukemia, Myeloid; Leukemia, Promyelocytic, Acute; Lymphoma; Macrolides; RNA, Messenger; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured

Topics: Cholecalciferol; Humans; Lymphoma; Skin; Skin Neoplasms; Sunscreening Agents; Ultraviolet Rays; Vitamin D

Topics: Aged; Animals; Antineoplastic Agents; Child, Preschool; Cholecalciferol; Humans; Hypocalcemia; Leukemia, Lymphoid; Lymphoma; Male; Neoplasms; Phosphates; Uric Acid