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Boron containing compound (BCC) offers the potential further development for therapy against malignant cancers.We successfully synthesized a new compound based on curcumin structure (curcumin analogue) containing boronatoms, namely, CCB-2 and revealed its cytotoxic activities on various cancer cell lines. The compound was simplysynthesized based on aldol condensation using acetone and 4-formylphenyl boronic acid resulted a symmetry CCB-2.The compound was then tested for cytotoxic activities in several cell lines. CCB-2 demonstrated cytotoxic effect onMCF-7/HER-2, MCF-7, RAW 264.7, and 4T1 with IC50 value of 12 µM, 54 µM, 26 µM, and < 10 µM, respectively,while less toxic in fibroblast cells. This compound performed superior cytotoxic against highly metastatic cancer cell,4T1. In addition, CCB-2 induced cells accumulation in G2/M phase, but decreased the accumulation of intracellularReactive oxygen species level in 4T1 cells. All the data suggest that this new compound is promising to be developedas anti-cancer agent rather than for Boron Neutron Capture Therapy-based cancer therapy
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Objective: To identify commonly regulated genes in HPV-infected HeLa and CaSki cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: HeLa and CaSki cells were treated with 2 × EC
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Objective:To identify commonly regulated genes in HPV-infected HeLa and CaSki cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1A-pentadiene-3-one (MS17) and to explore potential mechanisms that underfie its eytotoxic,anti-proliferative and apoptotic activity,Methods:HeLa and CaSki cells were treated with 2 × EC5o and 3 × EC50 doses of MS 17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling.Pair-wise significant genes (false discovery rate-corrected,P＜0.05)were analysed for fold change (FC) compared to control samples.Differentially expressed genes with FC≥2.0 (up-regulated;FC≥2.0 and down-regulated;FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile.Mutually regulated genes were ranked by FC and categorised by gene ontology.Results:Our data indicated dose-dependent regulation by MS 17 and identified top 20 mutually upand down-regulated genes each in HeLa and CaSki cells.Amongst these 17 were commonly regulated in both cell lines.These include the up-regulation of CCL26,DEFB103B,IL1RL1,LY96,GCNT3,MMPI0,MMP3,GADD45G and HSPA6,and the down-regulation of TENM2,NEBL,KIFC1,CTDSP1,IGFBP5,LTBP1,NREP and MXD3.These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS 17 in cervical cancer cells such as immune response,metabolic processes,proteolysis,programmed cell death,unfolded protein response,cell adhesion,cytoskeletal organisation,phosphatase activity,signal transduction and transcription regulator activity.Conclusions:Identification of seventeen common genes modulated by MS 17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS 17 in cervical cancer.
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Gamavuton-0 (GVT-0) is a curcumin analogue, which is synthesized from acetone and vanillin with chloride acid as a catalyst and ethanol as a solvent. The compound has been reported to have an anti-inflammatory effect related to its activity as COX-2 inhibitor, anti-oxydant, and radical scavanger. This study was aimed to investigate whether the GVT-0 has a suppressive effect on rheumatoid arthritis (RA) as one of chronic inflammatory disorders in a rat model. Wistar rats were immunized with Complete Freund’s Adjuvant (CFA). After a second CFA immunization, the rats were treated with GVT-0 orally at 10, 20, 40, 80 mg/kg BW once a day for 21 days, while the positive control received methotrexate 0.22 mg/kg BW. The animal paws were evaluated macroscopically for redness, swelling and deformities with Smit method to assess arthritic index. The anti-inflammatory effect of GVT-0 was evaluated using a plethismograph by measuring rat paw edema, while it’s effects on the level of TNF- and IL-1β in the ankle joints were examined using an ELISA method. The effect of GVT-0 on cartilage destruction was assesed histologically using Safranin-O staining. The acute toxicity test was also performed to assess the safety potential of the compound. The oral treatment of rats for 21 days with various doses of GVT-0 significantly suppressed the progession of RA indicated by the improvement of arthritic index and decreased the inflammation in rat paws. The compound also decreased the level of TNFα and IL-1β in ankle joints. The destruction of cartilage was significantly reduced in rats ankles after treatment with GVT-0. In toxicological assay, the apparent LD50 value of GT-0 was regarded as 7,29 g/kg BW and was classiefied to be practically non-toxic. The results suggest that GVT-0 is safe and potential to modify the progression of rheumatoid arthritis and can be developed as a new disease modifying anti rheumatoid arthritis drugs (DMARDs).
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Gamavuton-0 (GVT-0), a curcumin analogue, has been reported to have antiinflammatory and antioxidant activity, however, its analgesic activity has not yet been investigated. This research purpose is to study the effect of GVT-0 on acute and persistent pain using Modified Hot Plate (MHP) method and Formalin test, respectively, on male Swiss mice. In MHP method, the five groups of animals were pretreated with GVT-0 (10, 20, 40, and 80 mg/kg, orally) and indomethacin (4 mg/kgBB, i.p, for positive control), respectively, and immediately followed by stimulation with the carrageenan in sterile saline with a final volume of 50 μl in the left paw. The animals were then placed in hot plate (51oC). The latency time was determined at 90 min post-challenge. In the Formalin test, the six groups of animals were pretreated with GVT-0 (10, 20, 40 and 80 mg/kg, orally), morphine (5 mg/kgBB, i.p), and indomethacin (4 mg/kgBB, i.p) respectively, 60 min prior to the injection of 1.0% aqueous formalin (20 μl) administered by the intraplantar route into the right hindpaw. The licking time was measured at the first 5 min (initial phase, neurogenic) and 10-30 min after formalin injection (late phase, inflammatory). Result showed that GVT-0 has analgesic effect on acute pain using MHP method with ED50 of 27,69 mg/kgBW (p.o). While using Formalin test, GVT-0 showed analgesic activity with ED50 of 109,02 mg/kgBW (p.o) in initial phase, and ED50 of 13,53 mg/kgBW (p.o) in late phase. These results suggest that GVT-0 is a potential candidate for new antiinflammatory and analgesic agent that can be used for the treatment of different painful condition.