Kaempferol 3-O-rutinoside from Antidesma acidum Retz. Stimulates glucose uptake through SIRT1 induction followed by GLUT4 translocation in skeletal muscle L6 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Antidesma acidum Retz, a perennial herb is known for its anti-diabetic potential among the traditional health care providers of the tribal communities of Manipur, India. Scientific validation of the ancient knowledge on traditional use of this plant with the help of modern tools and techniques can promote further research and its use in health care. AIM OF THE STUDY: Type 2 Diabetes (T2D) is a complex metabolic disorder and linked with hyperglycemia occurring from insufficiency in insulin secretion, action, or both. The aim of this study was to scientifically validate the traditional myth behind the uses of this plant material against diabetes. More specifically, it was aimed to determine the effect of methanolic extract of A. acidum leaves and/or any of its bioactive phytochemical(s), in enhancing insulin sensitization and subsequently stimulating the insulin signaling cascade of glucose metabolism. MATERIALS AND METHODS: Methanol was used for extraction from the leaf powder of A. acidum followed by bioactivity guided fractionation and isolation of most active component. Biological evaluation was performed to determine the glucose uptake ability against insulin resistance in skeletal muscle (L6) cells. To understand the detailed mechanism of actions of the purified compound, several molecular biology and structural biology experiments such as Western blot, siRNA transfection assay and molecular docking study were performed. RESULTS AND DISCUSSION: Bioactivity guided isolation of pure compound and spectral data analysis led us to identify the active component as Kaempferol 3-O-rutinoside (KOR) for the first time from the leaf of A. acidum. Over expression of NAD-dependent histone deacetylase, Sirtuin 1 (SIRT1) was observed following KOR treatment. SIRT1 plays an important role in the metabolic pathway and over expression of SIRT implies that it involves in insulin signaling directly or indirectly. Molecular docking and simulation study showed the strong involvement between KOR and SIRT1.Treatment with KOR resulted in significant over expression of SIRT1followed by upregulation of insulin-dependent p-IRS, AKT and AMPK signaling molecules, and stimulation of the GLUT4 translocation, which ultimately enhanced the glucose uptake in sodium palmitate-treated insulin resistant L6 myotubes. Further, the effect of KOR on IRS1, AKT and AMPK phosphorylation, GLUT4 translocation, and glucose uptake was attenuated in SIRT1-knockdown myotubes. CONCLUSION: Overall, the results of this study suggest that Kaempferol 3-O-rutinoside is the active component presents in the leaf of A. acidum which increases glucose consumption by inducing SIRT1 activation and consequently improves insulin sensitization. These results may find future applications in drug discovery research against T2DM.

Chemical composite of indigenous whole grain scented joha rice varietal prevents type 2 diabetes in rats through ameliorating insulin sensitization by the IRS-1/AKT/PI3K signalling cascade.

Preventive measures to lower the prevalence of type-2 diabetes development using dietary phytochemicals are most realistic. A phytochemical composite derived from whole grain scented joha rice (PCKJ), which is indigenous to the North-eastern Region, India, was investigated to understand its preventive efficacy in rats in which type 2 diabetes was induced using a high-fat high-fructose (HFHF) diet and a low dose of streptozotocin, and the findings were correlated with those in L6-myotubes. Studies on cultured L6 myotubes revealed that treatment with PCKJ facilitated glucose uptake and GLUT-4 translocation to the plasma membrane, as evidenced by confocal microscopy and/or cell fractionation studies. Furthermore, the FFA-induced L6 myotubes were identified as having elevated levels of PI3K, p-AKT (Ser473) and GLUT-4, which returned to the basal level upon exposure to PCKJ. The administration of PCKJ (100 mg per kg body weight, oral gavage, 24 weeks) to rats significantly reduced their blood glucose levels along with common lipid and liver biomarkers (LDL, triglycerides, cholesterol, ALT, and AST) compared to the control group. Moreover, immunoblotting analysis showed that upon PCKJ treatment, PI3K, p-AKT and GLUT-4 levels are upregulated in the skeletal tissue of HFHF-fed rats, similar to the in vitro model. The alteration in the levels of inflammatory cytokines IL-6, IL-10 and IFN-γ in diabetic rats returned to normal levels upon exposure to PCKJ. Histological analysis of vital tissues further strengthens the findings of the preventive value of PCKJ against the development of insulin resistance. In conclusion, this study showed the prophylactic effect of PCKJ as a potent chemical composite, which can be used to develop functional foods (nutraceuticals) for ameliorating type-2 diabetes by improving insulin sensitization and thereby glucose metabolism.

Pharmacologically active chemical composite of Musa balbisiana ameliorates oxidative stress, mitochondrial cellular respiration, and thereby metabolic dysfunction.

The ripe fruit pulp of different Musa species is known for its excellent source of nutrient contents. Musa balbisiana (MB) is one such variety of Musa species, mainly found in the southern part of Asia, especially in the North-eastern part of India, remains unexplored despite its continuous use by the local traditional healers. The present study focuses on identifying and quantifying the active chemicals present in the ripe fruit pulp of Musa balbisiana (RFPMB) to understand its combined efficacy and nutritional benefit to control human metabolic complications specially related to diabetes and cardiovascular disorder. Characterization and confirmation through targeted LC-MS and HPLC-PDA based assays followed by quantitative analysis led us to identify the major bioactive compounds in RFPMB as shikimic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, sinapic acid, caffeic acid, syringic acid, chlorogenic acid, trans-cinnamic acid, and two essential fatty acids; linolenic acid and linoleic acid. The ripe fruit pulp is further analyzed to understand the nutritional and mineral content and found a substantial presence of calcium and potassium (15.74 ± 0.43 and 395.20 ± 9.5 mg/100 g of raw pulp, respectively) compared to other reported varieties. The active portion of RFPMB reduces the production of ROS, the expression of inflammatory marker genes TNF-α and TGF-ß, and accelerates the mitochondrial oxygen consumption rate (OCR) by enhancing the basal respiration, maximal respiration, and ATP production capacity of the targeted cells. The present study concluded that, a particular phytopharmaceutical composition of RFPMB with 11-biomarker compounds might be an efficacious formulation for developing a value-added nutraceutical product in managing metabolic complications and its related oxidative stress. PRACTICAL APPLICATIONS: This study has provided the prior information regarding the potential nutraceutical and phytochemical advantages of Musa balbisiana (MB) fruit pulp over other reported banana varieties. The HPLC-based quantification will give a clear understanding of the food values in comparison of bioactive compounds present in the active fraction of RFPMB, which can be an effective phytopharmaceutical in combating metabolic disorders and oxidative stress. Overall this study will help to commercialize a value-added product from this variety of banana with proper scientific validation.

Dietary phytochemicals/nutrients as promising protector of breast cancer development: a comprehensive analysis.

Genetic change, particularly epigenetic alteration, is one of the imperative factors for sporadic breast cancer development in the worldwide population of women. The DNA methylation process is essential and natural for human cellular renewal and tissue homeostasis, but its dysregulation contributes to many pathological changes, including breast tumorigenesis. Chemopreventive agents mainly protect the abnormal DNA methylation either by hindering the division of pre-malignant cells or looming the DNA damage, which leads to malignancy. The present review article is about understanding the potential role of dietary phytochemicals in breast cancer prevention. Accordingly, a literature search of the published article until August 2021 has been performed. Further, we have investigated the binding affinity of different phytochemicals isolated from diverse dietary sources against the various oncogenic proteins related to breast cancer initiation to understand the common target(s) in breast cancer prevention mechanisms. Various small phytochemicals, especially dietary phytochemicals including sulforaphane, mahanine, resveratrol, linolenic acid, diallyl sulfide, benzyl/phenethyl isothiocyanate, etc. are being investigated as the chemopreventive agent to manage breast cancer development, and some of them have shown promising outcomes in the cited research. In this present review, we discuss the recent advancement in acceptance of such types of potential dietary phytochemicals as a chemopreventive agent against breast cancer development and their inner lining mechanism. The critical clinical trials and cohort studies have also been considered to understand the progress in contemporary perspectives.

Astragalin mediates the pharmacological effects of Lysimachia candida Lindl on adipogenesis via downregulating PPARG and FKBP51 signaling cascade.

Metabolic disturbances in different tissue cells and obesity are caused by excessive calorie intake, and medicinal plants are potential sources of phytochemicals for combating these health problems. This study investigated the role of methanolic extract of the folklore medicinal plant Lysimachia candida (LCM) and its phytochemical, astragalin, in managing obesity in vivo and in vitro. Administration of LCM (200 mg/kg/body weight) daily for 140 days significantly decreased both the body weight gain (15.66%) and blood triglyceride and free fatty acid levels in high-fat-diet-fed male Wistar rats but caused no substantial change in leptin and adiponectin levels. The protein expression of adipogenic transcription factors in visceral adipose tissue was significantly reduced. Further, the 3T3-L1 cell-based assay revealed that the butanol fraction of LCM and its isolated compound, astragalin, exhibited antiadipogenic activity through downregulating adipogenic transcription factors and regulatory proteins. Molecular docking studies were performed to depict the possible binding patterns of astragalin to adipogenesis proteins. Overall, we show the potential antiobesity effects of L. candida and its bioactive compound, astragalin, and suggest clinical studies with LCM and astragalin.

Evaluation of therapeutic effect of Premna herbacea in diabetic rat and isoverbascoside against insulin resistance in L6 muscle cells through bioenergetics and stimulation of JNK and AKT/mTOR signaling cascade.

BACKGROUND: Premna herbacea Roxb., a perennial herb is well documented for its therapeutic uses among the traditional health care-givers of Assam, India. Scientific validation on the traditional use of the medicinal plant using modern technology may promote further research in health care. PURPOSE: This study evaluates the therapeutic potential of methanolic extract of P. herbacea (MEPH) against type 2 diabetes mellitus (T2DM) and its phytochemical(s) in ameliorating insulin resistance (IR), thereby endorsing the plant bioactives as effective anti-hyperglycemic agents. METHODS: The anti-diabetic potential of the plant extract was explored both in L6 muscle cells and high fructose high fat diet (HF-HFD) fed male Sprague Dawley (SD) rats. Bioactivity guided fractionation and isolation procedure yielded Verbascoside and Isoverbascoside (ISOVER) as bioactive and major phytochemicals in P. herbacea. The bioenergetics profile of bioactive ISOVER and its anti-hyperglycemic potential was validated in vitro by XFe24 analyzer, glucose uptake assay and intracellular ROS generation by flourometer, FACS and confocal microscopy. The potential of ISOVER was also checked by screening various protein markers via immunoblotting. RESULTS: MEPH enhanced glucose uptake in FFA-induced insulin resistant (IR) L6 muscle cells and decreased elevated blood glucose levels in HF-HFD fed rats. Isoverbascoside (ISOVER) was identified as most bioactive phytochemical for the first time from the plant in the Premna genus. ISOVER activated the protein kinase B/AMP-activated protein kinase signaling cascades and enhanced glucose uptake in IR-L6 muscle cells. ISOVER decreased the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) and increased that of mammalian target of rapamycin (mTOR), thereby attenuating IR. However, molecular docking revealed that ISOVER increases insulin sensitivity by targeting the JNK1 kinase as a competitive inhibitor rather than mTOR. These findings were further supported by the bioenergetics profile of ISOVER. CONCLUSION: This study for the first time depicts the functional properties of ISOVER, derived from Premna herbacea, in ameliorating IR. The phytochemical significantly altered IR with enhanced glucose uptake and inhibition of ROS through JNK-AKT/mTOR signaling which may pave the way for further research in T2DM therapeutics.

Effect of multiple doses of N-methyl-N-nitrosourea, an end product of methylguanidine (found in processed food), on the fertility of female Swiss albino mice.

Methylguanidine, an originator of carcinogenic methylnitrosourea, has been found in many animal meats and processed stored food often in high concentration. The present study was designed to understand the multiple dose effect of N-methyl-N-nitrosourea (MNU), an end product of methylguanidine, in Swiss albino mice fertility as well as cancer induction. Accordingly, a total of five experimental groups of animal (female Swiss albino mice) were taken, considering group-I as vehicle control and group-II-V as treatment groups (whereas group-II-Vwere treated with single to quadruple doses of 50 mg/kg of MNU respectively in a three weeks interval). After accomplishment of MNU injection, each female mice was mated with male mice to check the fertility efficiency. The results of the study indicated that, mice treated with highest number of MNU doses were 42.85% less efficient in getting pregnant than the control mice. There were noted changes in body weight, food and water intake upon MNU-exposure compared to control group. A significant increase in cumulative weight of vital female organs like uterus and ovary were also observed in mice injected with quadruple doses of MNU (50 mg/kg) compared to control mice. The findings of the study suggest the direct effect of MNU in pregnancy, without any cancer incidence in the vital female organs of Swiss albino mice.

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.

Assessment of nutritional value and quantitative analysis of bioactive phytochemicals through targeted LC-MS/MS method in selected scented and pigmented rice varietals.

Scented (joha) and black rice indigenous to northeast region (NER) of India are the two among 40,000 varieties of species Oryza sativa, prevalent for its great aroma, medicinal property, and/or equally noteworthy taste. Biochemical and target-based liquid chromatography mass spectrometry (LCMS) analysis was performed to identify and quantify the different phytonutrients from the selected rice grains of those two varieties. Biochemical assay revealed that the selected black rice (Chakhao Amubi) contains ∼1.8-fold higher amount of total phenolic and ∼2.3-fold higher amount of total flavonoid than the scented rice grain (Kon joha). The total starch content was significantly lower in scented rice in comparison to black rice grain. The health beneficial ratio of ω-6/ω-3 essential unsaturated fatty acid is notably better in scented rice grain than black rice grain. The targeted LC-MS/MS analysis confirms the presence of oryzanol and ferulic acid in both the samples. The presence of 4-hydroxy benzoic acid, apigenin, tricin, avenasterol, coumarin, coumaric acid, phenyl alanine, caffeic acid, and α-tocophenol were confirmed in the scented rice, whereas the black rice confirms the presence of protocatechuic acid and dehydroxy myricetin. Further the quantitative analysis showed that the lipids lysophosphatidylinositol (LPI) 16:0, lysophosphatidyl ethanolamine (LPE) 14:0, lysophosphatidyl choline (LPC) 18:2, LPE 18:2, phosphatidyl etanolamine (PE), along with oryzanol, hydroxy docosanoic acid are at least threefold higher in scented rice varietal; whereas, in Chakhao Amubi, the content of petunidin galactoside, LMMPE18:2, PC14:0 are higher than the scented rice grain. In conclusion, different phytonutrients including phenol, polyphenol, and flavonoid have been identified as bioactive phytochemicals in selected rice varietals. PRACTICAL APPLICATION: This work will provide the information about the nutritional benefit of studied rice varietals. The used targeted LC-MS/MS analysis will provide the one-step information about the bioactive phytochemicals. Overall, this study will help to commercialize those varieties with proper scientific evidences.

Ricinus communis L. fruit extract inhibits migration/invasion, induces apoptosis in breast cancer cells and arrests tumor progression in vivo.

Medicinal plant-based therapies can be important for treatment of cancer owing to high efficiency, low cost and minimal side effects. Here, we report the anti-cancer efficacy of Ricinus communis L. fruit extract (RCFE) using estrogen positive MCF-7 and highly aggressive, triple negative MDA-MB-231 breast cancer cells. RCFE induced cytotoxicity in these cells in dose and time-dependent manner. It also demonstrated robust anti-metastatic activity as it significantly inhibited migration, adhesion, invasion and expression of matrix metalloproteinases (MMPs) 2 and 9 in both cell lines. Further, flow cytometry analysis suggested RCFE-mediated induction of apoptosis in these cells. This was supported by attenuation of anti-apoptotic Bcl-2, induction of pro-apoptotic Bax and caspase-7 expressions as well as PARP cleavage upon RCFE treatment. RCFE (0.5 mg/Kg body weight) treatment led to significant reduction in tumor volume in 4T1 syngeneic mouse model. HPLC and ESI-MS analysis of active ethyl acetate fraction of RCFE detected four compounds, Ricinine, p-Coumaric acid, Epigallocatechin and Ricinoleic acid. Individually these compounds showed cytotoxic and migration-inhibitory activities. Overall, this study for the first time demonstrates the anti-cancer efficacy of the fruit extract of common castor plant which can be proposed as a potent candidate for the treatment of breast cancer.

Mahanine, A dietary phytochemical, represses mammary tumor burden in rat and inhibits subtype regardless breast cancer progression through suppressing self-renewal of breast cancer stem cells.

Mahanine (MH), a carbazole alkaloid isolated from an edible plant (Murraya koenigii), potentially inhibits the growth of altered subtypes of breast cancer cells in vitro and significantly reduced the mammary tumor burden in N-Methyl-N-nitrosourea (MNU) induced rat. The experimental results showed that 20-25 µM of MH for 24 h of treatment was very potent to reduce the cell proliferation through apoptosis with arresting the cells in G0/G1 in both ER+/p53WT MCF-7 and triple negative/p53Mut MDA-MB-231 cells. On the other hand, 10-15 µM of MH exposure to those two cell lines, caused inhibition of mammosphere formation and reduction of CD44high/CD24low/epithelial-specific antigen-positive (ESA+) population, which ultimately led to loss of self-renewal ability of breast cancer stem cells. Further, in vivo observation indicated that intraperitoneal injection of MH for four weeks with a dose of 50 mg/kg body weight thrice in a week, significantly (P =  0.03) reduced the mammary tumor weight in MNU induced rat. In conclusion, this study provides the novel insight into the mechanism of MH mediated growth arrest in subtype irrespective breast cancer progression.

Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling.

Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca2+ signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca2+-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca2+ leakage from ER and subsequently Ca2+ signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation.

Phytochemical portfolio and anticancer activity of Murraya koenigii and its primary active component, mahanine.

Murraya koenigii, a plant belonging to the Rutaceae family is widely distributed in Eastern-Asia and its medicinal properties are well documented in Ayurveda, the traditional Indian system of medicine. Through systematic research and pharmacological evaluation of different parts of the plant extracts has been shown to possess antiviral, anti-inflammatory, antioxidant, antidiabetic, antidiarrhoeal, antileishmanial, and antitumor activity. In the plant extracts, carbazole alkaloid, mahanine has been identified as the principle bioactive component among several other chemical constituents. Scientific evidence derived not only from in vitro cellular experiments but also from in vivo studies in various cancer models is accumulating for the pronounced anticancer effects of mahanine. The primary objective of this review is to summarize research data on cytotoxic chemical constituents present in different parts of Murraya koenigii and the anticancer activity of mahanine along with the recent understanding on the mechanism of its action in diverse cancer models. The information on its bioavailability and the toxicity generated from the recent studies have also been incorporated in the review.

Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma.

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.

Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo.

Pancreatic cancer is almost always fatal, in part because of its delayed diagnosis, poor prognosis, rapid progression and chemoresistance. Oncogenic proteins are stabilized by the Hsp90, making it a potential therapeutic target. We investigated the oxidative stress-mediated dysfunction of Hsp90 and the hindrance of its chaperonic activity by a carbazole alkaloid, mahanine, as a strategic therapeutic in pancreatic cancer. Mahanine exhibited antiproliferative activity against several pancreatic cancer cell lines through apoptosis. It induced early accumulation of reactive oxygen species (ROS) leading to thiol oxidation, aggregation and dysfunction of Hsp90 in MIAPaCa-2. N-acetyl-L-cysteine prevented mahanine-induced ROS accumulation, aggregation of Hsp90, degradation of client proteins and cell death. Mahanine disrupted Hsp90-Cdc37 complex in MIAPaCa-2 as a consequence of ROS generation. Client proteins were restored by MG132, suggesting a possible role of ubiquitinylated protein degradation pathway. Surface plasmon resonance study demonstrated that the rate of interaction of mahanine with recombinant Hsp90 is in the range of seconds. Molecular dynamics simulation showed its weak interactions with Hsp90. However, no disruption of the Hsp90-Cdc37 complex was observed at an early time point, thus ruling out that mahanine directly disrupts the complex. It did not impede the ATP binding pocket of Hsp90. Mahanine also reduced in vitro migration and tube formation in cancer cells. Further, it inhibited orthotopic pancreatic tumor growth in nude mice. Taken together, these results provide evidence for mahanine-induced ROS-mediated destabilization of Hsp90 chaperone activity resulting in Hsp90-Cdc37 disruption leading to apoptosis, suggesting its potential as a specific target in pancreatic cancer.

Identification and quantification of the active component quercetin 3-O-rutinoside from Barringtonia racemosa, targets mitochondrial apoptotic pathway in acute lymphoblastic leukemia.

Barringtonia racemosa has been used as a traditional medicine for the treatment of various diseases. The antitumor property of the seed extract of this plant in mice model promotes us to search for the active component present in the fruit extract. Quercetin 3-O-rutinoside (QOR) has been isolated from the fruits of this plant for the first time and quantified by HPLC method. The compound was identified by IR, mass, and NMR (1D, 2D) spectral data analysis. QOR showed dose- and time-dependent anti-proliferative activity in several leukemic cell lines with negligible effect on normal human peripheral blood mononuclear cell (PBMC). A representative T-lineage acute lymphoblastic leukemia cell line (MOLT-3) showed phosphatidyl serine externalization and DNA fragmentation, indicating QOR-induced programmed cell death. We established that QOR-induced apoptosis occurred preferentially on accumulation of cells in the sub-G(0) phase and genomic DNA fragmentation through the activation of mitochondria-dependent caspase cascade for the first time in T-lineage ALL cell line.