|Description:||1. Mahanine has a dose- and time-dependent anti-proliferative activity in acute lymphoid (MOLT-3) and chronic myeloid (K562) leukemic cell lines.|
2. Mahanine has effects on the activation of the apoptotic pathway in human leukemia U937 cells, causes the mitochondrial membranes to lose their permeability, resulting in caspase-3 activation and apoptosis.
3. Mahanine can reverse an epigenetically silenced gene, RASSF1A in prostate cancer cells by inhibiting DNMT activity that in turn down-regulates a key cell cycle regulator, cyclin D1, is an encouraging therapeutic choice for advanced prostatic cancer.
4. Mahanine inhibited growth of PC3 and LNCaP prostate cancer cells in a dose and time-dependent manner, inhibits growth and induces apoptosis in both androgen-responsive, LNCaP and androgen-independent, PC3 cells by targeting cell survival pathway.
|Targets:||JAK | Src | STAT | ROS | Chk | CDK | Akt | PI3K | p53|
|Source:||The leaves of Murraya koenigii|
|Solvent:||Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.|
|Storage:||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
Need more advice on solubility, usage and handling? Please email to: email@example.com
|After receiving:||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.|
|1 mg||5 mg||10 mg||20 mg||25 mg|
|1 mM||2.8777 mL||14.3885 mL||28.777 mL||57.554 mL||71.9424 mL|
|5 mM||0.5755 mL||2.8777 mL||5.7554 mL||11.5108 mL||14.3885 mL|
|10 mM||0.2878 mL||1.4388 mL||2.8777 mL||5.7554 mL||7.1942 mL|
|50 mM||0.0576 mL||0.2878 mL||0.5755 mL||1.1511 mL||1.4388 mL|
|100 mM||0.0288 mL||0.1439 mL||0.2878 mL||0.5755 mL||0.7194 mL|
Cancer Lett. 2014 Aug 28;351(1):81-90.
|Improved chemosensitivity in cervical cancer to cisplatin: synergistic activity of mahanine through STAT3 inhibition.[Pubmed: 24831030]|
|Toxicity reduction of cisplatin is necessary for improved treatment of cancer. Here we have demonstrated the synergistic growth-inhibitory effect of cisplatin on cervical cancer cells in-combination with a nontoxic herbal carbazole alkaloid, Mahanine. Mahanine enhanced cisplatin-induced apoptosis and reduced its effective concentration ∼5-8 folds. Mahanine inhibited JAK1 and Src and subsequently promoted proteasome-mediated degradation of STAT3. This event was further enhanced in-combination with cisplatin and subsequently inhibited cancer cell migration. Collectively, our results revealed that Mahanine may be a prospective agent to reduce the concentration of cisplatin in adjunct for the treatment of cancer and thereby decreasing its toxicity.|
Am J Cancer Res. 2014 Nov 19;4(6):629-47.
|Mahanine, a novel mitochondrial complex-III inhibitor induces G0/G1 arrest through redox alteration-mediated DNA damage response and regresses glioblastoma multiforme.[Pubmed: 25520856]|
|The Electron transport chain (ETC) is responsible for oxidative phosphorylation-mediated mitochondrial respiration. Here we wanted to address the Mahanine-induced targeted pathways in glioblastoma multiforme (GBM) in the context of G0/G1 phase arrest and redox alteration. We have demonstrated Mahanine, as a novel mitochondrial complex-III inhibitor which induced G0/G1 phase arrest in GBM. This event was preceded by accumulation of intracellular ROS by the inhibition of mitochondrial ETC. The accumulated ROS induced DNA damage response (DDR), that mediated Chk1/Chk2 upregulation and activation which were essential factors for the G0/G1 arrest. NAC-mediated scavenging of ROS generation reduced the propensity of G0/G1 phase arrest in GBM cells by Mahanine. Knockdown of Chk1/Chk2 also affected the cell cycle inhibitory potential of Mahanine. During G0/G1 arrest, other hallmark proteins like, cyclin D1/cyclin D3, CDK4/CDK6 and CDC25A were also downregulated. The G0/G1 phase restriction property of Mahanine was also established in in vivo mice model. Mahanine-induced complex-III inhibition triggered enhanced ROS in hypoxia responsible for higher G0/G1 arrest. Furthermore, we demonstrated that Mahanine-treated G0/G1 arrested cells were less potent to form xenograft tumor in vivo. Additionally, they exhibited reduced ability to migrate and form intracellular tube-like structures. Moreover, they became susceptible to differentiate and astrocyte-like cells were generated from the epithelial lineage. Taken together, our results established that complex-III of ETC is one of the possible potential targets of Mahanine. This nontoxic chemotherapeutic molecule enhanced ROS production, induced cell cycle arrest and thereafter regressed GBM without effecting normal astrocytes.|
J Med Chem. 2013 Jul 25;56(14):5709-21.
|Mahanine, a DNA minor groove binding agent exerts cellular cytotoxicity with involvement of C-7-OH and -NH functional groups.[Pubmed: 23829449]|
|Mahanine, a carbazole alkaloid is a potent anticancer molecule. To recognize the structure-activity correlation, Mahanine was chemically modified. Antiproliferative activity of these derivatives was determined in 19 cancer cell lines from 7 different origins. Mahanine showed enhanced apoptosis compared to dehydroxy-Mahanine-treated cells, indicating significant contribution of the C-7-OH group. O-Methylated-Mahanine and N-methylated dehydroxy-Mahanine-treated cells exhibited apoptosis only at higher concentrations, suggesting additional contribution of 9-NH group. Using biophysical techniques, we demonstrated that Mahanine interacts with DNA through strong association with phosphate backbone compared to other derivatives but is unable to induce any conformational change in DNA, hence suggesting the possibility of being a minor groove binder. This was corroborated by molecular modeling and isothermal titration calorimetry studies. Taken together, the results of the current study represent the first evidence of involvement of C-7-OH and 9-NH group of Mahanine for its cytotoxicity and its minor groove binding ability with DNA.|
Mol Cancer. 2013 Aug 30;12(1):99.
|Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells.[Pubmed: 24001151]|
|BACKGROUND: Hypermethylation of the promoter of the tumor suppressor gene RASSF1A silences its expression and has been found to be associated with advanced grade prostatic tumors. The DNA methyltransferase (DNMT) family of enzymes are known to be involved in the epigenetic silencing of gene expression, including RASSF1A, and are often overexpressed in prostate cancer. The present study demonstrates how Mahanine, a plant-derived carbazole alkaloid, restores RASSF1A expression by down-regulating specific members of the DNMT family of proteins in prostate cancer cells. RESULTS: Using methylation-specific PCR we establish that Mahanine restores the expression of RASSF1A by inducing the demethylation of its promoter in prostate cancer cells. Furthermore, we show that Mahanine treatment induces the degradation of DNMT1 and DNMT3B, but not DNMT3A, via the ubiquitin-proteasome pathway; an effect which is rescued in the presence of a proteasome inhibitor, MG132. The inactivation of Akt by wortmannin, a PI3K inhibitor, results in a similar down-regulation in the levels DNMT1 and DNMT3B. Mahanine treatment results in a decline in phospho-Akt levels and a disruption in the interaction of Akt with DNMT1 and DNMT3B. Conversely, the exogenous expression of constitutively active Akt inhibits the ability of Mahanine to down-regulate these DNMTs, suggesting that the degradation of DNMT1 and DNMT3B by Mahanine occurs via Akt inactivation. CONCLUSIONS: Taken together, we show that Mahanine treatment induces the proteasomal degradation of DNMT1 and DNMT3B via the inactivation of Akt, which facilitates the demethylation of the RASSF1A promoter and restores its expression in prostate cancer cells. Therefore, Mahanine could be a potential therapeutic agent for advanced prostate cancer in men when RASSF1A expression is silenced.|
Apoptosis. 2014 Jan;19(1):149-64.
|Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma.[Pubmed: 24052409]|
|5-Fluorouracil (5-FU) alone or in combination with other drugs is the main basis of chemotherapeutic treatment in colorectal cancer although patients with microsatellite instability generally show resistance to 5-FU treatment. The present investigation is focussed on the mechanistic insight of a pure herbal carbazole alkaloid, Mahanine, as a single or in combination with 5-FU in colon cancer. We demonstrated that Mahanine-induced apoptosis involved reactive oxygen species (ROS)-mediated nuclear accumulation of PTEN and its interaction with p53/p73. Mahanine and 5-FU in combination exerted synergistic inhibitory effect on cell viability. This combination also enhanced ROS production, increased tumour suppressor proteins and suppressed chemo-migration. Taken together, our results revealed that Mahanine can be a potential chemotherapeutic agent with efficacy to reduce the concentration of toxic 5-FU in colon cancer.|