tretinoin and tanshinone

To observe the effects of Tanshinone II A (Tan II A) on acute promyelocytic leukemia (APL) characterized by resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).. A 21-year-old male patient with relapsed APL, who previously received the maintenance therapy with ATRA,ATO, 6-Mercaptopurine (6-MP) and Methotrexate (MTX) for 1 year, was given Tan II A 80 mg intravenously once a day, and the changes of hematological parameters and side effects of Tan II A were observed.. The patient reached morphologically complete remission after using Tan II A intravenously for 54 days. During Tan II A treatment, obvious side effect was not observed.. Tan II A treatment may be effective in relapsed APL cases with ATRA and ATO resistance.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Humans; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Oxides; Tretinoin; Young Adult

To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice.. The mice osteoporosis was induced by given retinoic acid intragastrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after the mice were given TAN at the dose of 40, 80, 160 mg x kg(-1) respectly.. Tanshinone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group.. Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

Topics: Abietanes; Alkaline Phosphatase; Animals; Bone Density; Disease Models, Animal; Drugs, Chinese Herbal; Female; Humans; Male; Mice; Osteoporosis; Phenanthrenes; Tretinoin

To investigate the effect of tanshinone II A on the procoagulant activity (PCA) of human umbilical vein endothelial cells (HUVEC) induced by acute promyelocytic leukemia (APL) cell line NB4 cells.. The HUVEC were incubated for 6, 12, and 24 hours in different tanshinone II A conditioned medias (Tan II A-NB4-24h-CM, Tan II A-NB4-72h-CM, Tan II A-NB4-120h-CM). Then the HUVEC were incubated for 6, 12, 24, and 72 hours with Tan II A-NB4-120h-CM and different concentrations of Tan II A (0, 0.25, 0.5, 1.0 microg/mL). The HUVEC lysates were obtained by three repeated freezing and thrawing. Their PCA were tested using the one stage clotting assay. The activity of tissue factor (TF : act) was tested using the chromogenic substrate assay. The control groups included 0.3 microg/mL ATRA, 0.01% DMSO and RPMI 1640.. Tan II A-(72 h,120 h)-NB4-CM elevated PCA of HUVEC and six hours of incubation in the 120 h-NB4-CM had the greatest PCA. The PCA of HUVEC in the 1.0 microg/mL Tan II A-NB4-CM was the same as in the 0.3 microg/mL ATRA-NB4-CM. (2) The NB4-CM induced PCA of HUVEC decreased with 5.0 microg/mL of Tan II A, at a level similar to the decrease with 0.3 microg/mL of ATRA. Less than 5.0 microg/mL of Tan II did not reduce the NB4-CM induced PCA of HUVEC. (3) Both Tan II A 120 h-NB4-CM and ATRA 120 h-NB4-CM elevated the TF : act of HUVEC. The TF : act reached the peak after 6 hours of incubation. The Tan II A 120 h-NB4-CM maintained the peak level of TF : act at the 12th hour and fell to the base line at the 24th hour. The ATRA 120 h-NB4-CM induced TF:act dropped down with time after reaching its peak at the 6th hour. (4) The 1.0 microg/mL of Tan II A did not reduce the TF : act of HUVEC induced by the Tan II A 120 h-NB4-CM. But the 0.3 microg/mL of ATRA reduced the TF : act of HUVEC at the 6th hour.. TanIIA-NB4-CM increases PCA and TF : Act of HUVEC. TanIIA decreases PCA of HUVECs induces by TanIIA-NB4-CM.

Topics: Abietanes; Blood Coagulation Factors; Cell Line, Tumor; Endothelial Cells; Humans; Leukemia, Promyelocytic, Acute; Phenanthrenes; Thromboplastin; Tretinoin; Umbilical Veins

To evaluate the synergism of Tanshinone II A (Tan II A) and arsenic trioxide (As2O3) on the apoptosis of retinoic acid resistant acute promyelocytic leukemia (APL) cell line (MR2), and to investigate its effect on the expression of P-glycoprotein (Pgp) of MR2 cells.. As2O3 was added in the media of MR2 cells in a dose of 0.5 micromol/L, 2.0 micromol/L and 5.0 micromol/L, respectively, or combined with Tan II A in a dose of 1.0 microg/ml. The cell proliferation activity was assessed with MTT assay. The cell apoptosis was demonstrated by labeled Annexin V/PI method. The expression of Pgp was evaluated by immunocytochemical assay.. The MR2 cell proliferation activity was obviously inhibited in the two groups of As2O3 0.5 micromol/L, 2.0 micromol/L combined with Tan II A. The inhibitory effect gradually increased with the time extension. In 168 hours, the inhibitory rate of the two combination groups was (90.67+/-5.52)% and (86.70+/- 3.04)%, respectively, significantly stronger than that of corresponding dose of As2O3 alone group (P<0.01). The apoptosis effect of MR2 cell also gradually increased. In 168 hours, the apoptosis rate of the two combination groups was (81.52+/-7.23)% and (90.75+/-6.44)%, respectively, significantly stronger than that of corresponding dose of As2O3 alone group (P<0.01). At the same time, As2O3 alone and combination with Tan II A therapy can significantly reduce the MR2 cell Pgp expression (P<0.01).. There were apoptosis synergism on MR2 cell induced by Tan II A combined with As2O3, at the same time reduced the expression of Pgp in the cells.

Topics: Abietanes; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Arsenic Trioxide; Arsenicals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Synergism; Humans; Leukemia, Promyelocytic, Acute; Oxides; Phenanthrenes; Tretinoin

To investigate the effects of Tanshinone IIA (Tan IIA) on procoagulant activity (PCA) of human ECV304 cells induced by acute promyelocytic leukemia cell line NB4 cells.. ECV304 monolayers were respectively incubated for different hours at 37 degrees C in the conditioned media (CM) of NB4 cells treated with 0.5 microg/mL Tan IIA(Tan IIA-NB4-CM), 0.3 microg/mL all-trans retinoidic acid (ATRA)(ATRA-NB4-CM), DMSO(DMSO-NB4-CM) or the RPMI1640 medium. ECV304 lysates were tested for PCA using the one-stage clotting assay as well as for tissue factor activity (TF: Act) using the chromogenic substrate assay; ECV304 cell monolayers were incubated for different hours at 37 degrees C in a medium system including 0.5 microg/mL Tan IIA and Tan IIA-NB4-CM, and the ECV304 cell lysates were tested for PCA in the same way as above. Also they were controlled by 0.3 microg/mL ATRA, DMSO or RPMI1640 medium.. (1) The conditioned mediums from 0. 5 microg/mL Tan IIA that treated NB4 cells for 24, 72 and 120 hours respectively could elevate PCA of ECV cells, and this capability developed with the time of reaction. ATRA did the same as Tan IIA (P > 0.05). (2) 0.5 microg/mL Tan IIA down-regulated the PCA of ECV304 cells induced by Tan IIA-NB4-CM, and the inhibitory effects increased with time, reaching the highest at 120 hours. (3) Tan IIA120 h-NB4-CM up-regulated TF:Act of ECV304 cells, and the effect increased with time. (4) 0. 5 microg/mL Tan IIA down-regulated PCA and TF: Act of ECV304 cells induced by Tan IIA-NB4-CM, and the inhibitory effect increased with time; simultaneously, the test was controlled with 0.3 microg/mL ATRA, the effects on PCA and TF: Act were not significantly different (P > 0.05).. Tan IIA-NB4-CM can increase the levels of PCA and TF: Act of ECV304 cells through some unidentified factor; however, Tan IIA can obviously decrease the PCA and TF: Act levels of ECV304 cells induced by Tan IIA-NB4-CM.

Topics: Abietanes; Anticoagulants; Cell Differentiation; Cell Line; Cell Line, Tumor; Culture Media, Conditioned; Drugs, Chinese Herbal; Endothelial Cells; Humans; Leukemia, Promyelocytic, Acute; Phenanthrenes; Thromboplastin; Tretinoin; Umbilical Veins

A 30 years-old man was administrated with dizziness and fatigue for half month, and the big toe on his left foot got the prolonged bleeding of wound complicated with fever 7 days before the admission. The physical examination (PE) discovered that the case suffered from the anemic appearance, lower part tenderness of sternum, petechiae and purpura on skin of lower extremities, and with remaining not to be remarkable. The examination of blood routine showed WBC 2.3 x 10(9)/L, Hb 60/L, BPC 34 x 10(9)/L and blasts 0. 85. The bone marrow smear indicated markedly the hypercellularity, promyelocytes 89% and strongly positive myeloperoxidase (MPO). The PT and APTT were prolonged, and the FDP and D-dimer were positive. The acute promyelocytic leukemia (APL) with DIC was diagnosed. The patient was administered with all-trans retinoic acid (ATRA) with dosage of 20 mg three times per day. After 14 week treatment, the patient did not get complete remission. Then the tanshinone II A was taken orally with 30mg twice each day. After 8 week treatment of tanshinone II A, the blood routine was restored to normal. Four weeks later, the bone marrow also became normally, and the patient got a complete remission (CR). After more than 3 months of consolidation therapy with tanshinone II A, the patient was relapsed. When the homoharringtonine and cytarabine (HA) were given, the patient was got CR again. Three years later, he was relapsed secondarily, and then died of intracranial hemorrhage. The tanshinone II A could induce CR of APL with ATRA resistance, no side effect was observed; there is a reoccurring possibility from consolidation therapy with tanshinone II A.

Topics: Abietanes; Adult; Drug Resistance, Neoplasm; Humans; Leukemia, Promyelocytic, Acute; Male; Phenanthrenes; Remission Induction; Tretinoin

To investigate retinoic acid-resistant acute promyelocytic leukemia (APL) cell differentiation induced by tanshinone IIA (Tan IIA) and its molecular mechanism.. NB4 cells treated with 0.5 mg/L Tan IIA was regarded as positive control. After in vitro incubation of MR-2 cells with Tan IIA at the concentration of 1.0 mg/L for 4 days, the cell differentiation was observed by growth status, cytomorphology, and nitroblue tetrazolium test. Cell cycle, membrane cluster differentiation (CD) antigens (CD(33), CD(11b)) and expression of some oncogene (c-myc, c-fos, p53 and bcl-2) were analysed by flow cytometry.. The growth of MR-2 and NB4 cells was inhibited after Tan IIA treatment, the inhibition rate were 73.5% and 67.7% respectively (P < 0.01, P < 0.01) without significant difference. After Tan IIA treatment, MR-2 and NB4 cells were induced to undergo morphological differentiation, which exhibited small cell bulk decreased nucleus/cytoplasm proportion, rough chromatin, disappearance of nucleolus and formation of azurophil granules and anomalous nucleus. MR-2 cells could be induced to metamyelocyte while NB4 could be induced to band form. NBT reduction of MR-2 and NB4 cells treated with Tan IIA showed that positive cells accounted for (95.30 +/- 0.76)% and (93.20 +/- 1.04)% respectively; but the positive rate of either group of the treated positive cells was significantly higher than that of untreated, being (3.50 +/- 1.32)% and (2.80 +/- 0.29)% respectively (P < 0.01). Flow cytometry showed that the expression of CD(33) was reduced, while that of CD(11b) was increased. The quantity of treated cells in G(0)/G(1) phase increased but that in S phase decreased. The proliferous index was also decreased. After treated with Tan IIA, the expressions of anti-oncogene p53 and c-fos were up-regulated while those of oncogene bcl-2 and c-myc were down-regulated (P < 0.01).. 1.0 mg/L Tan IIA could inhibit proliferation of MR-2 cells and induce differentiation of MR-2 cells into mature granulocyte, the effectivity was the same as 0.5 mg/L Tan IIA treated NB4 cells. Its possible molecular mechanism might be related to modulation of oncogene expressions associated proliferation and differentiation as well as inhibition of DNA synthesis. Tan IIA probably can be applied to treat the patients with APL, particularly to the relapsed and drug resistant patients with broad prospect.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Leukemia, Promyelocytic, Acute; Phenanthrenes; Tretinoin

To evalutate the synergistic effects of Tanshinone II A combined with all-trans retinoic acid (ATRA) on the differentiation and apoptosis of human acute promyelocytic leukemia (APL) cell line (NB4).. The NB4 cells were treated with 0.5 microg/ml Tanshinone II A combined with 0.5 microg/ml, 0.25 microg/ml and 0.125 microg/ml ATRA respectively in culture. Cells differentiation was demonstrated by morphology and NBT reduction assay. The expression of CD11b and CD33, cell cycle and apoptosis induced by these drugs were measured by flow cytometry (FCM).. The proliferative inhibition rate of the combination of Tan II A with ATRA was much higher. The differentiated cells accounted for over 90 percent, among them the band forms and neutrophils constituted more than 65 percent. NBT reduction and CD11b expression were much higher, and expression of CD33 was lower than that of Tan II A or ATRA alone (P<0.01). FCM analysis also showed that combination of Tan II A with ATRA arrested NB4 cells in G0/G1 phase and induced significantly apoptosis of NB4 cells (P<0.01). There were no significant dose dependent effects induced by ATRA in combination with Tan II A at 0.125 microg/ml to 0.5 microg/ml on differentiation and apoptosis of NB4 cells.. The combination of Tan II A with ATRA has synergistic effects on differentiation and apoptosis of NB4 cells. The effects do not increase with the dosage escalation of ATRA.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Differentiation; Cell Line, Tumor; Drug Synergism; Drugs, Chinese Herbal; Humans; Leukemia, Promyelocytic, Acute; Phenanthrenes; Tretinoin

The differentiation-inducing activity of tanshinone (TAN) and all-trans-retinoic acid (RA) was studied in vitro on a human cervical carcinoma cell line, ME180. The tumor cells were treated with TAN or RA in DMSO (final concentration 0.02%, V/V) on 4 successive days. Cells treated with the same concentration of DMSO alone served as control. Morphologic studies with light and transmission electron microscopy showed that the cells treated with both TAN and RA became well-differentiated. The cell growth, (as revealed by cell counting and 3H-TdR incorporation) was inhibited and the tumorigenicity in nude mice was reduced. No significant difference was observed between the cells treated with TAN and RA.

Topics: Abietanes; Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Transformation, Neoplastic; Female; Humans; Mice; Mice, Nude; Phenanthrenes; Tretinoin; Tumor Cells, Cultured; Uterine Cervical Neoplasms