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Bhahwal Ali Shah - One of the best experts on this subject based on the ideXlab platform.
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interplay between cell cycle and autophagy induced by Boswellic Acid analog
Scientific Reports, 2016Co-Authors: Anup Singh Pathania, Parduman R. Sharma, Bhahwal Ali Shah, Santosh Kumar Guru, Suresh Kumar, Ashok Kumar, Masroor Ahmad, Shashi Bhushan, Priya Mahajan, Simmi SharmaAbstract:In this study, we investigated the role of autophagy induced by Boswellic Acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death.
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synthesis of β Boswellic Acid derivatives as cytotoxic and apoptotic agents
Bioorganic & Medicinal Chemistry Letters, 2016Co-Authors: Parduman R. Sharma, Bhahwal Ali Shah, Arvind Kumar, Arem Qayum, Shashank K SinghAbstract:A series of β-Boswellic Acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of apoptosis confirmed by loss of mitochondrial membrane potential, DAPI staining, Western blotting and ROS generation.
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PARP cleavage and perturbance in mitochondrial membrane potential by 3-α-propionyloxy-β-Boswellic Acid results in cancer cell death and tumor regression in murine models
Future Oncology, 2012Co-Authors: Yasrib Qurishi, Parduman R. Sharma, Bhahwal Ali Shah, Shashank K Singh, Abid Hamid, Zahoor Ahmad Wani, Dilip M. Mondhe, Mohmmad Afzal Zargar, Samar S. Andotra, Subhash C. TanejaAbstract:Background: Apoptotic induction in cancer cells has become a major focus of anticancer therapeutics. In this regard, β-Boswellic Acids, naturally occurring pentacyclic triterpenes, have demonstrated antiproliferative and cytotoxic effects against different types of cancers. Surprisingly, not much has been reported regarding the chemical modifications or preparation of structural analogs of the key constituents of β-Boswellic Acid. Aim: The anticancer activity of 3-α-propionyloxy-β-Boswellic Acid (POBA) was investigated and this article reports for the first time that the triterpenoid ring of the Boswellic Acid derivative POBA is targeting the PI3K pathway. Materials & methods: Induction of apoptosis of the semi-synthetic derivative of β-Boswellic Acid-POBA in vitro was analyzed using a battery of human cancer cell lines followed by cell cycle phase distribution, further validated by DNA fragmentation, and was found to cause mitochondrial membrane potential loss with ultrastructural changes, as observed by...
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a propionyloxy derivative of 11 keto β Boswellic Acid induces apoptosis in hl 60 cells mediated through topoisomerase i ii inhibition
Chemico-Biological Interactions, 2011Co-Authors: Gousia Chashoo, Bhahwal Ali Shah, Shashank K Singh, Abid Hamid, Dilip M. Mondhe, Samar S. Andotra, Paraduman R Sharma, A K Saxena, Naveed A Qazi, Subhash C. TanejaAbstract:Boswellic Acids have invariably been reported for their antiproliferative potential in various cell systems. In the present study the growth inhibitory effect of propionyloxy derivative of 11-keto-β-Boswellic Acid (PKBA; a semisynthetic analogue of 11-keto-β-Boswellic Acid) on HL-60 promyelocytic leukemia cells is being reported for the first time. In the preliminary studies, in vitro cytotoxicity of PKBA was investigated against eight human cancer cell lines viz., IMR-32, SF-295 (both neuroblastoma), PC-3 (prostate), Colo-205 (colon), MCF-7 (breast), OVCAR-5 (ovary), HL-60, Molt-4 (both leukemia) and their respective IC(50) values were found to be 5.95, 7.11, 15.2, 14.5, 15, 15.9, 8.7 & 9.5μg/ml, respectively. For determining the mechanism of cell death in HL-60 cells, PKBA was subjected to different mechanistic studies. DNA relaxation assay of PKBA revealed inhibition of both topoisomerases I & II. The fragmentation analysis of DNA revealed typical ladders indicating the cytotoxic effect to be mediated by induction of apoptosis. The morphologic studies of PKBA showed the presence of true apoptotic bodies. Apoptosis was confirmed further by flow-cytometric detection of sub-G(1) peaks and enhanced annexin-V-FITC binding of the cells. The activation of apoptotic cascade by PKBA in HL-60 cells was found to be associated with the loss of mitochondrial membrane potential, release of cytochrome c, activation of initiator and executioner caspases and cleavage of poly ADP ribose polymerase (PARP). In vivo studies of PKBA revealed anti-tumoral activity against both ascitic and solid murine tumor models. These studies thus demonstrate PKBA to induce apoptosis in HL-60 cells due to the inhibition of topoisomerases I and II.
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A comparative study of proapoptotic potential of cyano analogues of Boswellic Acid and 11-keto-Boswellic Acid.
European Journal of Medicinal Chemistry, 2011Co-Authors: Rajbir Kaur, Sheema Khan, Renu Chib, Tandeep Kaur, Parduman R. Sharma, Jaswant Singh, Bhahwal Ali Shah, Subhash C. TanejaAbstract:Semi-synthetic analogues of β-Boswellic Acid (BA) and 11-keto-β-Boswellic Acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies).
Rene Csuk - One of the best experts on this subject based on the ideXlab platform.
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new derivatives of 11 keto β Boswellic Acid kba induce apoptosis in breast and prostate cancers cells
Natural Product Research, 2019Co-Authors: Asma Bani Araba, Rene Csuk, Najeeb Ur Rehman, Hidayat Hussain, Amna Alaraimi, Sulaiman Alhashmi, Sulaiman Alshidhani, Ahmed Alharrasi, Fahad ZadjaliAbstract:A series of new 11-keto-β-Boswellic Acid were partially-synthesized by modifying the hydroxyl and carboxylic Acid functional groups of ring A. The structures of the new analogs were confirmed by de...
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Synthesis of new Boswellic Acid derivatives as potential antiproliferative agents
Natural Product Research, 2019Co-Authors: Umair Shamraiz, Rene Csuk, Najeeb Ur Rehman, Hidayat Hussain, Sulaiman Al-shidhani, Aasim Saeed, Husain Yar Khan, Ajmal Khan, Lucie Fischer, Amin BadshahAbstract:In the current investigation, a series of heterocyclic derivatives of Boswellic Acids were prepared along with new monomers of 3-O-acetyl-11-keto-β-Boswellic Acid (AKBA, 1) 11-keto-β-Boswellic Acid...
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Synthesis of new Boswellic Acid derivatives as potential antiproliferative agents
2019Co-Authors: Umair Shamraiz, Rene Csuk, Najeeb Ur Rehman, Hidayat Hussain, Sulaiman Al-shidhani, Aasim Saeed, Husain Yar Khan, Ajmal Khan, Lucie Fischer, Amin BadshahAbstract:In the current investigation, a series of heterocyclic derivatives of Boswellic Acids were prepared along with new monomers of 3-O-acetyl-11-keto-β-Boswellic Acid (AKBA, 1) 11-keto-β-Boswellic Acid (KBA, 2) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer 21 effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC50 values below 9 μM. In addition, compounds 7, 8, 11, 12, 15, 16, and 17 also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog 8 was highly cytotoxic for A375 cancer cells with an EC50 value of 2.1 μM.
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New derivatives of 11-keto-β-Boswellic Acid (KBA) induce apoptosis in breast and prostate cancers cells
2019Co-Authors: Asma Bani Araba, Rene Csuk, Ahmed Al-harrasi, Najeeb Ur Rehman, Hidayat Hussain, Sulaiman Al-shidhani, Amna Al-araimi, Sulaiman Al-hashmi, Fahad ZadjaliAbstract:A series of new 11-keto-β-Boswellic Acid were partially-synthesized by modifying the hydroxyl and carboxylic Acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds 4, 5 and 9 exhibited potent anti-cancer results against two human tumor cancer cell lines having IC50 value of MCF-7 (breast) and LNCaP (prostate): 123.6, 9.6 and 88.94 μM and 9.6, 44.12 and 12.03 μM, respectively. Additionally, a maximum nuclear fragmentation was observed for 4 (78.44%) in AKBA treated cells after 24 hr followed by 5 and 9 with (74.25 and 66.9% respectively). This study suggests that the presence of hydrazone functionality (4 and 9) has effectively improved the potency of AKBA. Interestingly, compound 5 with a lost carboxylic Acid group of ring A showed comparable potent activity. Highly selective AKBA requires further modification to improve its bioavailability and solubility inside the cancer cells.
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Formation of Boswellic Acid derivatives.
2018Co-Authors: Ahmed Al-harrasi, Najeeb Ur Rehman, Abdul Latif Khan, Muhammed Al-broumi, Issa Al-amri, Javid Hussain, Hidayat Hussain, Rene CsukAbstract:Formation of Boswellic Acid derivatives.
Areg Hovhannisyan - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of curcumin and its combination with Boswellic Acid in osteoarthritis a comparative randomized double blind placebo controlled study
BMC Complementary and Alternative Medicine, 2018Co-Authors: Armine Haroyan, Vahan Mukuchyan, Nana Mkrtchyan, Naira Minasyan, Srbuhi Gasparyan, Aida Sargsyan, Mikael Narimanyan, Areg HovhannisyanAbstract:The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with Boswellic Acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg Boswellic Acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients’ global assessment of disease severity. Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin® compared to placebo was observed both in physical performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin® group. The treatments were well tolerated. Twelve-week use of curcumin complex or its combination with Boswellic Acid reduces pain-related symptoms in patients with OA. Curcumin in combination with Boswellic Acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin® increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and Boswellic Acid. This trial is registered at the database www.clinicaltrials.gov . https://clinicaltrials.gov/ct2/show/NCT02390349?term=EuroPharma&rank=1 . Study registration number: NCT02390349 .
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Efficacy and safety of curcumin and its combination with Boswellic Acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study
BMC, 2018Co-Authors: Armine Haroyan, Vahan Mukuchyan, Nana Mkrtchyan, Naira Minasyan, Srbuhi Gasparyan, Aida Sargsyan, Mikael Narimanyan, Areg HovhannisyanAbstract:Abstract Background The aim of this clinical trial was to assess the efficacy and safety of curcuminoid complex extract from turmeric rhizome with turmeric volatile oil (CuraMed®) and its combination with Boswellic Acid extract from Indian frankincense root (Curamin®) vs placebo for the treatment of 40- to 70-year-old patients with osteoarthritis (OA). Methods The effects of CuraMed® 500-mg capsules (333 mg curcuminoids) and Curamin® 500-mg capsules (350 mg curcuminoids and 150 mg Boswellic Acid) taken orally three times a day for 12 weeks in 201 patients was investigated in a three-arm, parallel-group, randomized, double-blinded, placebo-controlled trial. Primary outcome efficacy measures included OA physical function performance-based tests, the WOMAC recommended index of joint pain, morning stiffness, limitations of physical function, and the patients’ global assessment of disease severity. Results Favorable effects of both preparations compared to placebo were observed after only 3 months of continuous treatment. A significant effect of Curamin® compared to placebo was observed both in physical performance tests and the WOMAC joint pain index, while superior efficacy of CuraMed vs placebo was observed only in physical performance tests. The effect size compared to placebo was comparable for both treatment groups but was superior in the Curamin® group. The treatments were well tolerated. Conclusions Twelve-week use of curcumin complex or its combination with Boswellic Acid reduces pain-related symptoms in patients with OA. Curcumin in combination with Boswellic Acid is more effective. Combining Curcuma longa and Boswellia serrata extracts in Curamin® increases the efficacy of OA treatment presumably due to synergistic effects of curcumin and Boswellic Acid. Trial registration This trial is registered at the database www.clinicaltrials.gov . https://clinicaltrials.gov/ct2/show/NCT02390349?term=EuroPharma&rank=1 . Study registration number: NCT02390349
Yongkui Jing - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of novel 2 substituted 11 keto Boswellic Acid heterocyclic derivatives as anti prostate cancer agents with pin1 inhibition ability
European Journal of Medicinal Chemistry, 2017Co-Authors: Shuxiang Wang, Yongkui Jing, Dan Liu, Linxiang ZhaoAbstract:A series of novel acetyl-11-keto-β-Boswellic Acid (AKBA) derivatives with a different electron-withdrawing group on ring A and a nitrogen heterocycle at C-24 were designed and synthesized. These semi-synthetic compounds showed improved anti-proliferative activity against prostate cancer cells over AKBA. Compound 8f bearing 2-cyano-3,11-dioxo moiety and piperazine was the most potent to inhibit growth of prostate cancer PC-3 (IC50 = 0.04 μM) and LNCaP (IC50 = 0.27 μM) cell lines. 8f caused cell cycle arrest in G2/M and induced apoptosis. 8f decreased the protein levels of anti-apoptosis protein Mcl-1, c-FLIP and cell cycle regulating protein cyclin D1. 8f inhibited the activity of Pin1, a peptidyl-prolyl cis-trans isomerase to stabilize cyclin D1. 8f represented a compound with improved anti-proliferative effects for prostate cancer therapy working through new mechanisms.
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acetyl keto β Boswellic Acid induces apoptosis through a death receptor 5 mediated pathway in prostate cancer cells
Cancer Research, 2008Co-Authors: Lijuan Xia, Huiming Hua, Yongkui JingAbstract:Acetyl-keto-beta-Boswellic Acid (AKBA), a triterpenoid isolated from Boswellia carterri Birdw and Boswellia serrata, has been found to inhibit tumor cell growth and to induce apoptosis. The apoptotic effects and the mechanisms of action of AKBA were studied in LNCaP and PC-3 human prostate cancer cells. AKBA induced apoptosis in both cell lines at concentrations above 10 microg/mL. AKBA-induced apoptosis was correlated with the activation of caspase-3 and caspase-8 as well as with poly(ADP)ribose polymerase (PARP) cleavage. The activation of caspase-8 was correlated with increased levels of death receptor (DR) 5 but not of Fas or DR4. AKBA-induced apoptosis, caspase-8 activation, and PARP cleavage were inhibited by knocking down DR5 using a small hairpin RNA. AKBA treatment increased the levels of CAAT/enhancer binding protein homologous protein (CHOP) and activated a DR5 promoter reporter but did not activate a DR5 promoter reporter with the mutant CHOP binding site. These results suggest that AKBA induces apoptosis in prostate cancer cells through a DR5-mediated pathway, which probably involves the induced expression of CHOP.
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Boswellic Acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells
Molecular cancer therapeutics, 2005Co-Authors: Lijuan Xia, Duo Chen, Rui Han, Qicheng Fang, Samuel Waxman, Yongkui JingAbstract:The mechanism of the cytotoxic effect of Boswellic Acid acetate, a 1:1 mixture of alpha-Boswellic Acid acetate and beta-Boswellic Acid acetate, isolated from Boswellia carterri Birdw on myeloid leukemia cells was investigated in six human myeloid leukemia cell lines (NB4, SKNO-1, K562, U937, ML-1, and HL-60 cells). Morphologic and DNA fragmentation assays indicated that the cytotoxic effect of Boswellic Acid acetate was mediated by induction of apoptosis. More than 50% of the cells underwent apoptosis after treatment with 20 mug/mL Boswellic Acid for 24 hours. This apoptotic process was p53 independent. The levels of apoptosis-related proteins Bcl-2, Bax, and Bcl-XL were not modulated by Boswellic Acid acetate. Boswellic Acid acetate induced Bid cleavage and decreased mitochondrial membrane potential without production of hydrogen peroxide. A general caspase inhibitor (Z-VAD-FMK) and a specific caspase-8 inhibitor II (Z-IETD-FMK) blocked Boswellic Acid acetate-induced apoptosis. The mRNAs of death receptors 4 and 5 (DR4 and DR5) were induced in leukemia cells undergoing apoptosis after Boswellic Acid acetate treatment. These data taken together suggest that Boswellic Acid acetate induces myeloid leukemia cell apoptosis through activation of caspase-8 by induced expression of DR4 and DR5, and that the activated caspase-8 either directly activates caspase-3 by cleavage or indirectly by cleaving Bid, which in turn decreases mitochondria membrane potential.
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Boswellic Acid acetate induces differentiation and apoptosis in leukemia cell lines
Leukemia Research, 1999Co-Authors: Lijuan Xia, Qicheng Fang, Samuel Waxman, Yongkui Jing, Shigeo Nakajo, Kusuyasu Nakaya, Rui HanAbstract:Boswellic Acid acetate (BC-4), a compound isolated from the herb Boswellia carterii Birdw., can induce differentiation and apoptosis of leukemia cells. Based on cell morphology and NBT reduction, BC-4 induced monocytic differentiation of myeloid leukemia HL-60, U937 and ML-1 cells at a dose under 12.5 microg/ml (24.2 microM). BC-4 was a potent inducer, with 90% of the cells showing morphologic changes and 80-90% of the cells showing NBT reduction. Specific and non-specific esterase were also increased by BC-4. Based on benzidine staining assay, BC-4 failed to induce erythroid leukemia DS-19 and K562 cells differentiation. In contrast to its selective differentiation effect, BC-4 strongly inhibited growth of all cell lines tested. The growth inhibition effect was dose- and time-dependent. In HL-60 cells, 20 microg/ml (38.8 microM) of BC-4 decreased viable cell number by 60% at 24 h, whereas at 3 days there was virtually no viable cells. Morphologic and DNA fragmentation analysis proved that BC-4 induced cell apoptosis. The dual apoptotic and differentiation effects of BC-4 suggest that it may be a powerful agent in the treatment of leukemia.
Zuhua Gao - One of the best experts on this subject based on the ideXlab platform.
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retracted acetyl 11 keto beta Boswellic Acid akba prevents human colonic adenocarcinoma growth through modulation of multiple signaling pathways
Biochimica et Biophysica Acta, 2013Co-Authors: Yi Yuan, Yan Wang, Hong-xiang Lou, Zuhua Gao, Shuxiang Cui, Ruiqi WangAbstract:BACKGROUND Acetyl-11-keto-beta-Boswellic Acid (AKBA) is a derivative of Boswellic Acid. We have previously reported that AKBA can reduce the number and size of colonic adenomatous polyps in the APC(Min/+) mouse model. In this study, we evaluated the effect of AKBA on human colonic adenocarcinoma growth. Its efficacy and toxicity were compared with those of the non-steroidal anti-inflammatory drug aspirin. METHODS The inhibition of cancer cell growth was estimated by colorimetric and clonogenic assay. Cell cycle distribution was analyzed by the flow cytometry assay. Annexin V-FITC/PI staining and JC-1 fluorescence probe assays were performed to determine the apoptotic cells. Further experiment was carried out in mice with HT-29 xenografts. AKBA was orally administered for 24days. The HT-29 xenografts were removed for TUNEL staining and western blotting analysis. Blood was obtained for clinical chemical analysis, and samples of organs were sectioned for microscopic assessment. RESULTS AKBA significantly inhibited human colon adenocarcinoma growth, showing arrest of the cell cycle in G1-phase and induction of apoptosis. AKBA administration in mice effectively delayed the growth of HT-29 xenografts without signs of toxicity. The activity of AKBA was more potent than that of aspirin. Western blotting suggested that this activity may arise from its multiple effects on the activation of apoptotic proteins, suppression of inflammatory cytokines and modulation of EGFR and ATM/P53 signaling pathways in the HT-29 xenografts. CONCLUSIONS AKBA prevents the growth of colonic adenocarcinoma through modulation of multiple signaling pathways. GENERAL SIGNIFICANCE AKBA could be a promising agent in the prevention of colonic adenocarcinomas.
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chemoprevention of intestinal adenomatous polyposis by acetyl 11 keto beta Boswellic Acid in apc min mice
International Journal of Cancer, 2013Co-Authors: Huiping Liu, Yan Wang, Zuhua Gao, Shuxiang Cui, Hong-xiang LouAbstract:Acetyl-11-keto-beta-Boswellic Acid (AKBA) is a derivative of Boswellic Acid, which is an active component of the gum resin of Boswellia serrata. AKBA has been used as an adjuvant medication for treatment of inflammatory diseases. In this study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent against intestinal adenomatous polyposis in the adenomatous polyposis coli multiple intestinal neoplasia (APCMin/+) mouse model. APCMin/+ mice were administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were sacrificed and the number, size and histopathology of intestinal polyps were examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small intestine and 60.4% in the colon. An even greater AKBA effect was observed in preventing the malignant progression of these polyps. The number of large (>3 cm) colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a significant reduction in the number of dysplastic cells and in the degree of dysplasia in each polyp after AKBA treatment. There was no evidence of high grade dysplasia or intramucosal carcinoma in any of the polyps examined within the treated group. More interestingly, interdigitated normal appearing intestinal villi were observed in the polyps of the treated group. During the course of the study, AKBA was well tolerated by the mice with no obvious signs of toxicity. Results from immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay indicated that the chemopreventive effect of AKBA was attributed to a collection of activities including antiproliferation, apoptosis induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its chemopreventive action through the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could be a promising regimen in chemoprevention against intestinal tumorigenesis.
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retracted acetyl 11 keto β Boswellic Acid akba inhibits human gastric carcinoma growth through modulation of the wnt β catenin signaling pathway
Biochimica et Biophysica Acta, 2013Co-Authors: Yusheng Zhang, Hong-xiang Lou, Ruiqi Wang, Jizhen Xie, Juliali Zhong, Yizhuo Qin, Zuhua GaoAbstract:BACKGROUND Acetyl-11-keto-beta-Boswellic Acid (AKBA) is a derivative of Boswellic Acid, an active component of Boswellia serrata gum resin. We examined the effect of AKBA on human gastric carcinoma growth and explored the underlying molecular mechanisms. METHODS Inhibition of cancer cell growth was estimated by colorimetric and clonogenic assays. Cell cycle distribution was analyzed by flow cytometry and apoptosis determined using Annexin V-FITC/PI staining and DNA ladder quantification. After three weeks of oral AKBA administration in nude mice bearing cancer xenografts, animals were sacrificed and xenografts removed for TUNEL staining and western blot analysis. RESULTS AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity. This effect might be associated with its roles in cell cycle arrest and apoptosis induction. The results also showed activation of p21(Waf1/Cip1) and p53 in mitochondria and increased cleaved caspase-9, caspase-3, and PARP and Bax/Bcl-2 ratio after AKBA treatment. Further analysis suggested that these effects might arise from AKBA's modulation of the aberrant Wnt/β-catenin signaling pathway. Upon AKBA treatment, β-catenin expression in nuclei was inhibited, and membrane β-catenin was activated. In the same sample, active GSK3β was increased and its non-active form decreased. Levels of cyclin D1, PCNA, survivin, c-Myc, MMP-2, and MMP-7, downstream targets of Wnt/β-catenin, were inhibited. CONCLUSIONS AKBA effects on human gastric carcinoma growth were associated with its activity in modulating the Wnt/β-catenin signaling pathway. GENERAL SIGNIFICANCE AKBA could be useful in the treatment of gastric cancers.