Effect Of Embelin Research Articles

Effect of embelin on inhibition of cell growth and induction of apoptosis in Acanthamoeba castellanii.

Acanthamoeba castellanii is the causative agent of fatal encephalitis and blinding keratitis. Current therapies remain a challenge, hence there is a need to search for new therapeutics. Here, we tested embelin (EMB) and silver nanoparticles doped with embelin (EMB-AgNPs) against A. castellanii. Using amoebicidal assays, the results revealed that both compounds inhibited the viability of Acanthamoeba, having an IC50 of 27.16 ± 0.63 and 13.63 ± 1.08μM, respectively, while causing minimal cytotoxicity against HaCaT cells in vitro. The findings suggest that both samples induced apoptosis through the mitochondria-mediated pathway. Differentially expressed genes analysis showed that 652 genes were uniquely expressed in treated versus untreated cells, out of which 191 were significantly regulated in the negative control vs. conjugate. Combining the analysis, seven genes (ARIH1, RAP1, H3, SDR16C5, GST, SRX1, and PFN) were highlighted as the most significant (Log2 (FC) value ± 4) for the molecular mode of action in vitro. The KEGG analysis linked most of the genes to apoptosis, the oxidative stress signaling pathway, cytochrome P450, Rap1, and the oxytocin signaling pathways. In summary, this study provides a thorough framework for developing therapeutic agents against microbial infections using EMB and EMB-AgNPs.

Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1\u03b2-stimulated human umbilical cord mesenchymal stem cells

Breast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.

Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation.

Embelin is a quinone derivative and found in the fruits of Embelia ribes Burm.f. Embelin has been identified as a small molecular inhibitor of X-chromosome-linked inhibitor of apoptosis proteins, and has multiple biological activities, including antioxidation, anti-inflammation, and antitumor effects. However, the effect of embelin in platelets remains unclear. Thus, this study investigated the antiplatelet mechanism of embelin. Our data revealed that embelin could inhibit platelet aggregation induced by various agonists, including the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Embelin, as well as the PKC inhibitor Ro 31-8220, markedly reduced PDBu-mediated phosphorylation of the PKC substrate, suggesting that embelin may be a PKC inhibitor for platelets. Embelin could block PKC downstream signaling and events, including the inhibition of protein kinase B and mitogen-activated protein kinase activation, granule release, and glycoprotein IIbIIIa activation. Moreover, embelin could delay thrombus formation in the mesenteric microvessels of mice, but did not significantly affect the tail bleeding time. In conclusion, we demonstrated that embelin is a PKC inhibitor and possesses antiplatelet and antithrombotic effects. The further analysis is necessary to more accurately determine clinical therapeutic potential of embelin in all clinical thromboembolic events with disturbance of thrombocyte function.

The Effect of Embelin's Physiological Activity as Cosmetics Ingredients

Objectives: Embelin has been used in various treatments for skin diseases have excellent efficacy and have beenwidely used in folk remedies. Therefore, we want to observe the possibility of embelin as an additive to cosmetics.Method: The cytotoxicity test was conducted to observe the safety of the component, and the antioxidantforce of the component itself was observed using a DPPH solution. The effects on ROS generation using DCFDAwere observed. We observed the potential as a inhibitor of NO produced by inflammatory reactions andmeasured tyrosinase activity and melanin production to observe the possibility of utilization as skin whitening.Findings: The results of observing the decimals using DPPH showed weak inhibition due to be weaklysuppressed. Antioxidants were observed using Raw 264.7 macrophage. It inhibited ROS production in thecells induced by silica. In particular, production was inhibited on a concentration-dependent basis. As aresult, the embelin has its own antioxidant function, has been shown to act as antioxidant in cells, and itsconcentration has inhibited NO production. Although the tyrosinase activity using L-dopa and L-tyrosine assubstrates did not have any significant effect, melanin production in melanin cells resulted in concentration- dependent suppression.Applications: Based on these results, it was found that embelin was highly antioxidant and was likely to beused as an anti-aging cosmetics ingredient.

Effect of Embelin in Monosodium Glutamate Induced Obesity in Male Neonatal Wistar Rats

Recent clinical studies report antipsychotics as a better option to augment the action of antidepressants in treatment resistant cases. However, the proper mechanisms underlying the antidepressant effect of antipsychotics is still not clear. Indolamine 2, 3 dioxygenase (IDO) pathway is considered to be an important pathway in pro-inflammatory cytokine associated stress-induced depression. The present study investigated the antidepressant effect of venlafaxine, olanzapine and their combinations in chronic forced-swim stress-induced depression in mice. In addition, the role of pro-inflammatory cytokines and IDO-mediated pathway was investigated. Swiss albino mice were subjected to chronic forced-swim stress and evaluation for antidepressant-like activity was performed on 7th, 14th and 21st day following which serum levels of pro-inflammatory cytokines (IL-1β and IL-6 levels) and the levels of hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5HT) were estimated. The combination exhibited augmentation of antidepressant-like activity of venlafaxine by olanzapine in chronic forced-swim stress model. Further, it reversed the enhanced serum IL-1β and IL-6 and reverted the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed mice. Augmentation of antidepressant effect of venlafaxine by olanzapine is thus mediated by normalising the shift from KYN to TRP pathway in chronic forced swim induced stressed mice.

Antidepressant-like effects of embelin and its possible mechanisms of action in chronic unpredictable stress-induced mice

Objectives Embelin, a principal active constituent of embelin ribes burm, has good therapeutic effects on various diseases. To explore the effects and underlying mechanisms of embelin on depression, we made a preliminary study to clarify this issue.Methods We first used chronic unpredictable stress (CUS) to construct the model of depression in mice. Then, we determined the effects of embelin on CUS-induced behavioral dysfunction using open field test, sucrose preference test, tail suspension test and forced swimming test. Furthermore, we used the biological experiments to evaluate the changes of brain-derived neurotrophic factor (BDNF), oxidative stress, neuronal inflammation and the hypothalamic pituitary adrenal (HPA) axis after embelin treatment.Results The behavioral tests indicated embelin indeed had efficient antidepressant effects. Moreover, enhanced BDNF expression, decreased oxidative stress markers (TBARS, nitric oxide) activities, elevated antioxidants (total thiol, catalase) expression, decreased pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) expression and normalized the HPA axis activity were found after embelin treatment in CUS-induced mice. Hence, the results of biological experiments confirmed the antidepressant-like effects of embelin.Discussion These results indicated that embelin can effectively suppress CUS-induced depressive-like behaviors through increasing BDNF expression, preventing brain from oxidative stress and neuronal inflammation, and normalizing the HPA activity.

Memory enhancing effect of embelin against scopolamine-induced amnesia in Sprague Dawley rats

Memory enhancing effect of embelin against scopolamine-induced amnesia in Sprague Dawley rats

Su2018 Macrophage Targeting Contributes to the Inhibitory Effects of Embelin on Colitis-Associated Cancer

Su2018 Macrophage Targeting Contributes to the Inhibitory Effects of Embelin on Colitis-Associated Cancer

Embelin-Induced Phosphatidylserine Translocation in the Erythrocyte Cell Membrane

Background/Aims: The antihelminthic, contraceptive, anti-inflammatory and anticancer phytochemical embelin is at least in part effective against malignancy by inducing suicidal death or apoptosis of tumor cells. Erythrocytes are similarly able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide formation, oxidative stress as well as activation of p38 kinase and protein kinase C (PKC). The present study tested, whether and how embelin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. Results: A 48 hours exposure of human erythrocytes to embelin (≥25 µM) significantly increased the percentage of annexin-V-binding cells and hemolysis. Embelin did not significantly modify [Ca²⁺]_i. The effect of embelin on annexin-V-binding was not blunted by removal of extracellular Ca²⁺, by p38 kinase inhibitor SB203580 (2 µM) or by PKC inhibitor staurosporine (1 µM). Embelin did, however, significantly increase the ceramide abundance. Conclusions: Embelin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect involving ceramide formation.

Embelin Suppresses Growth of Human Pancreatic Cancer Xenografts, and Pancreatic Cancer Cells Isolated from KrasG12D Mice by Inhibiting Akt and Sonic Hedgehog Pathways

Pancreatic cancer is a deadly disease, and therefore effective treatment and/or prevention strategies are urgently needed. The objectives of this study were to examine the molecular mechanisms by which embelin inhibited human pancreatic cancer cell growth in vitro, and xenografts in Balb C nude mice, and pancreatic cancer cell growth isolated from KrasG12D transgenic mice. XTT assays were performed to measure cell viability. AsPC-1 cells were injected subcutaneously into Balb c nude mice and treated with embelin. Cell proliferation and apoptosis were measured by Ki67 and TUNEL staining, respectively. The expression of Akt, and Sonic Hedgehog (Shh) and their target gene products were measured by the immunohistochemistry, and Western blot analysis. The effects of embelin on pancreatic cancer cells isolated from 10-months old KrasG12D mice were also examined. Embelin inhibited cell viability in pancreatic cancer AsPC-1, PANC-1, MIA PaCa-2 and Hs 766T cell lines, and these inhibitory effects were blocked either by constitutively active Akt or Shh protein. Embelin-treated mice showed significant inhibition in tumor growth which was associated with reduced expression of markers of cell proliferation (Ki67, PCNA and Bcl-2) and cell cycle (cyclin D1, CDK2, and CDK6), and induction of apoptosis (activation of caspase-3 and cleavage of PARP, and increased expression of Bax). In addition, embelin inhibited the expression of markers of angiogenesis (COX-2, VEGF, VEGFR, and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues. Antitumor activity of embelin was associated with inhibition of Akt and Shh pathways in xenografts, and pancreatic cancer cells isolated from KrasG12D mice. Furthermore, embelin also inhibited epithelial-to-mesenchymal transition (EMT) by up-regulating E-cadherin and inhibiting the expression of Snail, Slug, and ZEB1. These data suggest that embelin can inhibit pancreatic cancer growth, angiogenesis and metastasis by suppressing Akt and Shh pathways, and can be developed for the treatment and/or prevention of pancreatic cancer.

Effect of embelin in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Objective: Cerebral ischemia induced by stroke is one of the major causes of death and disability in the world and reactive oxygen species play key role in pathogenesis of cerebral ischemia. Chemical structure of embelin is similar to antioxidant coenzyme Q10 and embelin is reported to have potent antioxidant activity. Therefore, the present investigation is carried out to study the effect of embelin using the middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia model. Methods: Male Wistar rats were treated with embelin (50, 75 and 100 mg/kg, p.o.) for 20 days, followed by MCAO-induced focal cerebral ischemia. Measurement of neurological score, infarct size and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in brain homogenates were carried out at the end of study. Results: Embelin decreases MDA level whereas increases SOD and CAT level as compared to ischemic control group. Moreover, embelin decreases infarct size, but there was no improvement in neurological score. Conclusion: Pretreatment of embelin enhances the antioxidant defense and thereby ameliorates cerebral ischemia/reperfusion induced injury in the rat MCAO model.

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway.

Brain glioma is the most common malignant intracranial tumor and has become the focus of research on diseases of the central nervous system due to its high incidence and poor prognosis. As a small‑molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), embelin has the ability to specifically inhibit XIAP to control and regulate the apoptosis of various types of tumor cells. However, to date, the mechanism of action for this effect is not well understood. The aim of this study was to investigate the role that the mitochondrial pathway plays in embelin-induced brain glioma cell apoptosis and the effect of embelin on the cell cycle. Brain glioma cells were treated with different doses of embelin. The MTT method was used to determine cell proliferation, and flow cytometry was used to determine apoptosis, as well as changes in the cell cycle and cell mitochondrial membrane potential. Western blot analysis was performed to determine the expression levels of apoptosis‑associated proteins, Bcl-2, Bcl-xL, Bax and Bak as well as cytochromec. We found that embelin induced a time‑ and dose‑dependent apoptosis of brain glioma cells, and that it could arrest the cell cycle in the G0/G1 phase. Embelin also caused changes in brain glioma cell mitochondrial membrane potential. Additionally, embelin regulated the shifting of Bax and Bcl-2 to promote the mitochondrial release of cytochromec, thus activating the caspase proteins to cause apoptosis. Thus, embelin induces apoptosis in brain glioma cells which is closely associated with the mitochondrial pathway.

Embelin accelerates cutaneous wound healing in diabetic rats

This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat.

Embelin-induced MCF-7 breast cancer cell apoptosis and blockade of MCF-7 cells in the G2/M phase via the mitochondrial pathway

Embelin is a small molecular inhibitor extracted from Myrsinaceae plants that specifically inhibits XIAP, affecting the proliferation and apoptosis of various types of tumor cells. In our previous studies, we have demonstrated that embelin is able to induce the apoptosis of MCF-7 breast cancer cells in a dose-dependent manner. However, its mechanism of action is not yet clear. The purpose of this study was to investigate the involvement of the mitochondrial pathway in embelin-induced apoptosis and the effect of embelin on the cell cycle. Different doses of embelin were added to MCF-7 breast cancer cells and it was found that embelin was able to induce apoptosis of MCF-7 breast cancer cells in a dose- and time-dependent manner. Flow cytometry analysis revealed that embelin caused changes in the MCF-7 cell mitochondrial membrane potential and blocked the cell cycle of MCF-7 cells in the G2/M phase. Moreover, embelin was demonstrated to promote mitochondrial release of cytochrome C via regulation of Bax and Bcl-2, resulting in the activation of caspase-3 and -9, while no significant changes in the level of caspase-8 were observed. The results have demonstrated that embelin-induced apoptosis of MCF-7 breast cancer cells involves the mitochondrial pathway.

Embelin-induced apoptosis of HepG2 human hepatocellular carcinoma cells and blockade of HepG2 cells in the G2/M phase via the mitochondrial pathway

Embelin is a small-molecule inhibitor extracted from plants of the Myrsinaceae family demonstrating specific inhibition of the X-linked inhibitor of apoptosis protein (XIAP) to affect the proliferation and apoptosis of various types of tumor cells. However, the mechanism of action for this effect remains unclear. The purpose of the present study was to investigate the role of the mitochondrial pathway in embelin-induced HepG2 human hepatocellular carcinoma cell apoptosis and the effect of embelin on the cell cycle. HepG2 human hepatocellular carcinoma cells were treated with different doses of embelin. The MTT method was used to determine cell viability, and flow cytometry was used to assess the rate of apoptosis and the changes in mitochondrial membrane potential; the cell cycle was also analyzed. Western blot analysis was performed to determine the expression levels of the apoptosis-associated proteins Bax, Bcl-2 and the caspase family. The results revealed that embelin induced the apoptosis of the HepG2 cells in a dose- and time-dependent manner. In addition, embelin caused changes in mitochondrial membrane potential. Flow cytometric analysis demonstrated that embelin caused blockade of the HepG2 cells in the G2/M phase of the cell cycle.

Inhibition of UVB-induced oxidative damage and apoptotic biochemical changes in human lymphocytes by 2,5-dihydroxy-3-undecyl-1,4-benzoquinone (embelin)

Purpose: The present study investigates the inhibition of Ultraviolet B (UVB, 290–320 nm) radiation-induced oxidative damage in peripheral blood human lymphocytes by embelin extracted from Embelia ribes.Materials and methods: Embelin was extracted, purified and characterized. Prior to inhibitory assessment, a maximum concentration of embelin that was non-toxic was determined. Six experimental groups, including respective controls were made to assess the inhibitory effect of embelin for the selected concentrations of 10 and 20 μg/ml. For the experimental groups; lymphocytes (1 × 106 cells) were pre-treated with the chosen concentration of embelin for a period of 60 min and then exposed to UVB for 30 min. UVB radiation inhibitory effect of embelin assessed by measuring antioxidant and lipid peroxidation levels, deoxyribonucleic acid (DNA) damage, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) at scheduled time points after irradiation.Results: Pre-treatment of lymphocytes with embelin prevents UVB-induced oxidative damage. An increase in antioxidant levels in irradiated cells in the presence of embelin and UV absorbance of embelin could be the reason for the decrease in lipid peroxidation level and prevention of DNA damage by UVB radiation.Conclusion: Embelin prevents oxidative stress induced by UVB irradiation via its antioxidant property.

Abstract 1709: The effect of a XIAP inhibitor, embelin, on apoptosis of thyroid cancer cell lines

Abstract X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis (IAP) protein family that selectively blocks caspases-3, -7, -9 and inhibits cell death. Embelin, a XIAP inhibitor, is known to exhibit anti-inflammatory and apoptotic activities. Recent reports suggest that embelin interferes the signal transducer and activator of transcription 3 (STAT3) pathway and nuclear factor-kB (NF-kB) signal pathway. In this study, we investigated the anti-cancer efficacy of embelin by measuring its effects on apoptosis of thyroid cancer cell lines. We also explored the mechanism underlying these effects. We found that embelin induced the apoptosis of human thyroid cancer cell lines, such as FTC-133, CAL-62, KTC-1, and 8505C. The effect was stronger in BRAF V600E-mutant thyroid cancer cell lines (KTC-1 and 8505C) than wild-type cell lines (FTC-133 and CAL-62). The effect of embelin on cell apoptosis was associated with increased phosphorylation of p38. SB203580 inhibited the embelin mediated induction of cleaved caspase-3 activity in V600E mutant thyroid cancer cell lines. Interestingly, embelin induced apoptosis in BRAF wild type cancer cell lines, even after treatment of SB203580. These results indicated that another signaling pathway, not a p38 pathway, might be existed for embelin induced apoptosis in BRAF wild type thyroid cancer cell. In conclusion, embelin-induced XIAP suppression resulted in an increase of apoptosis via phosphorylation of p38 in BRAF V600E-mutant thyroid cancer cell lines. Regulation of XIAP activity may be potentially useful as a treatment of thyroid cancer, especially in BRAF V600E-mutant thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1709. doi:1538-7445.AM2012-1709

Effect of embelin on lithium–induced nephrogenic diabetes insipidus in albino rats

ObjectiveTo evaluate the nephroprotective and anti–polyuric role of embelin on lithium induced nephrogenic diabetes insipidus (NDI) in albino rats. MethodsNDI induced by lithium chloride (4 meq/kg/day, i.p. for 6 days) which leads to huge amount of urine excretion. After induction of NDI, embelin (50 and 100mg/kg) was administered orally, once daily for 21 day in rats and N–acetyl cysteine (10mg/kg, twice daily, i.p.) was used as a standard drug for treatment of NDI. The body weight, urine protein, urine creatinine, plasma creatinine, blood urea nitrogen were assessed at 0, 7, 14 and 21 day. At the end of the study glutathione (GSH) content in kidney was assessed and histopathology of kidney was performed. ResultsEmbelin 50 and 100 mg/kg showed increase in the body weight and decrease in plasma and urine creatinine, blood urea nitrogen levels, and urine protein level. Embelin acts as a potent antioxidant; it increases the level of glutathione in kidney. Histopathological examination of the kidney indicated that embelin 50 and 100 mg/kg were reduced the vascular degeneration of tubules as well as slight degeneration and dilatation of renal tubules, however N–actyl cysteine (NAC) treated rats showed normal glomeruli and renal tubule with slight degeneration. ConclusionsEmbelin seemed to be effective in NDI by its predominant effect on promoting antioxidant status and decrease the urine excretion may be due to the blocking of sodium channels.

Inhibitor of XIAP Embelin reverses the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed

Objective To investigate whether safe doses of Embelin, a small-molecular weight inhibitor of X-linked inhibitor of apoptosis protein (XIAP) can reverse the resistance of human pancreatic carcinoma Patu8988 cell line to pemetrexed. Methods The effect of Embelin on growth inhibition of pemetrexed-resistant Patu8988 strain and its parent strain and half maximal inhibitory concentration ( IC50 ) of pemetrexed alone and its combination with Embelin for the growth of the two cell strains were determined by the cell counting Kit-8 assay. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the changes in the expression of XIAP mRNA and protein after the interference of Embelin. Results Embelin presented growth inhibition on both cell stains without significant differences in vitro in a dose-dependent manner. The maximal safe dose of Embelin for both strains was 2. 5 mg/L. Only in Patu8988 strain to pemetrexed was noted a significant difference in the IC50 value between pemetrexed alone and pemetrexed in combination with safe doses of Embelin. The expression of XIAP mRNA and protein was decreased by 33% and 25% respectively (P＜0. 05) in pemetrexed-resistant Patu8988 strain after the interference of Embelin. Flow cytometry analysis showed that the apoptosis rate of drug-resistant cells treated with pemetrexed in combination with Embelin was higher than that of cells treated with pemetrexed alone [ (38.73±2.55)% vs (25. 87 ±2.81)%, P＜0.05]. Conclusion Embelin can reduce the the higher expression of XIAP mRNA and protein levels in drug-resistant cells and increase the sensitivity of drug-resistant Patu8988 cell strain to pemetrexed, but has no significant effect on parental Patu8988 strain. Key words: Pancreatic carcinoma; Drug resistance; Embelin; Reverse

Antiproliferative Properties of Embelia ribes

Embelia ribes is a threatened woody shrub belonging to the family Myrsinaceae, which is sparsely distributed in the moist deciduous forests of the Western Ghats in India. The previous reports showed the effect of Embelin in methylcholanthrene induced fibrosarcoma in albino rats besides en- hancing their survival time. Embelin provided a good support for the chemopreventive effect against N- nitrosodiethy- lamine/ phenobarbital induced hepatocarcinogenesis in Wistar rats. The present studies on cancer cell lines revealed that the crude hexane extract of the fruits of Embelia ribes exhibited cytotoxicity against Human leukaemic cells (K562) and Dalton's Lymphoma ascites cells (DLA). Bioactivity directed fractionation and isolation yielded Embelin as the active principle. Invitro studies on Embelin suggests the potential of the compound on these two cell lines. However the compound did not exhibit toxicity on normal lymphocytes isolated from human blood preferentially attacking the tumour cells. This is the first report of invitro cytotoxic activity of Embelia ribes.