Anionic species from multivalent metal salts are differentially retained during aqueous ionic gelation of sodium alginate and could fine-tune the hydrogel properties.

The role of anionic counterions of divalent metal salts in alginate gelation and hydrogel properties has been thoroughly investigated. Three anions were selected from the Hofmeister series, namely sulphate, acetate and chloride, paired in all permutations and combinations with divalent metal cations like calcium, zinc and copper. Spectroscopic analysis revealed the presence of anions and their interaction with the respective metal cations in the hydrogel. The data showed that the gelation time and other hydrogel properties were largely controlled by cations. However, subtle yet significant variations in viscoelasticity, water uptake, drug release and cytocompatibility properties were anion dependent in each cationic group. Computational modelling based study showed that metal-anion-alginate configurations were energetically more stable than the metal-alginate models. The in vitro and in silico studies concluded that acetate anions preceded chlorides in the drug release, swelling and cytocompatibility fronts, followed by sulphate anions in each cationic group. Overall, the data confirmed that anions are an integral part of the metal-alginate complex. Furthermore, anions offer a novel option to further fine-tune the properties of alginate hydrogels for myriads of applications. In addition, full exploration of this novel avenue would enhance the usability of alginate polymers in the pharmaceutical, environmental, biomedical and food industries.

Transition Metal Dichalcogenides (TMDC)-Based Nanozymes for Biosensing and Therapeutic Applications.

Nanozymes, a type of nanomaterial with enzyme-like properties, are a promising alternative to natural enzymes. In particular, transition metal dichalcogenides (TMDCs, with the general formula MX2, where M represents a transition metal and X is a chalcogen element)-based nanozymes have demonstrated exceptional potential in the healthcare and diagnostic sectors. TMDCs have different enzymatic properties due to their unique nano-architecture, high surface area, and semiconducting properties with tunable band gaps. Furthermore, the compatibility of TMDCs with various chemical or physical modification strategies provide a simple and scalable way to engineer and control their enzymatic activity. Here, we discuss recent advances made with TMDC-based nanozymes for biosensing and therapeutic applications. We also discuss their synthesis strategies, various enzymatic properties, current challenges, and the outlook for future developments in this field.

Biofunctionalized cellulose paper matrix for cell delivery applications.

The present study delineates the preparation, characterization, and application of (3-Aminopropyl)triethoxysilane (APTES)/Caprine liver-derived extracellular matrix (CLECM) coated paper matrix for cell delivery. Here, we exploited positively charged surface of the paper matrix (as imparted by APTES derivatization) to improve the biological responses of the cells. Our results demonstrated that the functionalized paper matrixes favored the adhesion, growth, and proliferation of multiple cell types including normal, transformed, cancerous, and stem cells as compared to the pristine paper matrix. Upon implantation into the mice model, the developed paper matrix supported infiltration of the host cells and vasculature without showing any evidence of significant systemic toxicity. Moreover, the cells cultured on the paper matrix, when delivered to the CAM and mouse models, showed an enhanced vascular network around the substrate, thereby confirming its potential to deliver the cells in vivo. Together, the study confirms that the reported paper-based platform is easy to fabricate, cheap, portable and could efficiently be applied to cell delivery applications for either tissue repair or the development of humanized animal model.

Membrane perturbation through novel cell-penetrating peptides influences intracellular accumulation of imatinib mesylate in CML cells.

Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. The use of first- and second-generation tyrosine kinase inhibitors has been successful to an extent. However, resistance against such drugs is an emerging problem. Apart from several drug-resistant mechanisms, drug influx/efflux ratio appears to be one of the key determinants of therapeutic outcomes. In addition, intracellular accumulation of drug critically depends on cell membrane fluidity and lipid raft dynamics. Previously, we reported two novel cell-penetrating peptides (CPPs), namely, cationic IR15 and anionic SR11 present in tryptic digest of Abrus agglutinin. Here, the potential of IR15 and SR11 to influence intracellular concentration of imatinib has been evaluated. Fluorescent correlation spectroscopy and lifetime imaging were employed to map membrane fluidity and lipid raft distribution following peptide-drug co-administration. Results show that IR15 and SR11 are the two CPPs which can modulate membrane fluidity and lipid raft distribution in K562 cells. Both IR15 and SR11 significantly reduce the viability of CML cells in the presence of imatinib by increasing the intracellular accumulation of the drug.

Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death.

Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells. Additionally, it observed that AGG-induced autophagic cell death in Bax knock down (Bax-KD) and 5-FU resistant HeLa cells, confirming as an alternate cell killing pathway to apoptosis. At the molecular level, AGG-induced ER stress in PERK dependent pathway and inhibition of ER stress by salubrinal, eIF2α phosphatase inhibitor as well as siPERK reduced autophagic death in the presence of AGG. Further, our in silico and colocalization study showed that AGG interacted with pleckstrin homology (PH) domain of Akt to suppress its phosphorylation and consequent downstream mTOR dephosphorylation in HeLa cells. We showed that Akt overexpression could not augment GRP78 expression and reduced autophagic cell death by AGG as compared to pcDNA control, indicating Akt modulation was the upstream signal during AGG's ER stress mediated autophagic cell death. In conclusion, we established that AGG stimulated cell death by autophagy might be used as an alternative tumor suppressor mechanism in human cervical cancer. © 2016 Wiley Periodicals, Inc.

Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer.

Abrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki-67 and CD-31, respectively. In addition, TUNEL positive cells increased in breast tumors treated with AGG suggesting that AGG mediates anti-tumorigenic activity through induction of apoptosis and inhibition of angiogenesis. On a molecular level, AGG caused extrinsic apoptosis through ROS generation that was AKT-dependent in breast cancer cells, without affecting primary mammary epithelial cells, suggesting potential cancer specificity of this natural compound. In addition, using HUVECs, AGG inhibited expression of the pro-angiogenic factor IGFBP-2 in an AKT-dependent manner, reducing angiogenic phenotypes both in vitro and in vivo. Overall, the present results establish that AGG promotes both apoptosis and anti-angiogenic activities in human breast tumor cells, which might be exploited for treatment of breast and other cancers.

Cell penetrating peptides from agglutinin protein of Abrus precatorius facilitate the uptake of Imatinib mesylate.

Targeted drug delivery is of paramount importance for cancer patients. Cell penetrating peptides (CPPs) have emerged as potent vehicles for this purpose. Herein, we demonstrate CPP- like properties of two peptides: NH2-SGASDDEEIAR-COOH (SR11) and NH2-ICSSHYEPTVRIGGR-COOH (IR15), derived from the tryptic digest of Abrus precatorius agglutinin. Both IR15 and SR11 were found to be non-toxic at lower doses (up to 50 µg/ml). These two peptides entered into HeLa cells through lipid raft-mediated endocytosis within 15 min and penetrated the nuclear membrane in 60 min of incubation. Co-treatment of peptides (20 µg/ml) and Imatinib (5 µM) in HeLa cells increased uptake of the drug by ∼ 55% and lowered the IC50 value to one-third in comparison to the drug added exclusively. However, co-treatment of TAT peptide (standard CPP) did not alter the Imatinib uptake significantly. In summary, we have identified two novel CPPs from tryptic digest of Abrus agglutinin which increased the cellular uptake of Imatinib upon co-administration. Further studies may result in deciphering a novel mode of drug delivery.

Immune augmentation and Dalton's Lymphoma tumor inhibition by glucans/glycans isolated from the mycelia and fruit body of Pleurotus ostreatus.

With the increase in cancer progression, alternatives in the medicinal field with minimal side effects need to be ascertained. In this context, for the first time novel glucans/glycans isolated from the mycelia and fruit body of Pleurotus ostreatus have been compared for their exquisite property as immunoceuticals. Glucans from both the sources displayed immunological functions which include lymphocyte proliferation, macrophage activation (nitric oxide production, ROS generation, phagocytosis, TNF-α production) as well as macrophage and NK cell mediated cytotoxicity. In vivo studies with Dalton's Lymphoma mice tumor model further enumerated the immune enhancing and tumor regression potential of the two glucan molecules. Highest tumor inhibition of about 75% and 71.4% were observed at 20mg/kg of mycelia and fruit body glucan/glycan treatments. A concomitant increase in the survival period of glucan treated tumor bearing mice was found to be primarily associated with immune boosting and apoptosis of cancerous cells. Both the glucan molecules exhibited similar degree of immune response at the systemic level with only subtle amount of differences in two dimensional in vitro cultures. Efficacy of glucans/glycans as immunomodulators may thereby provide decisive leads in strengthening the immune system along with other therapies.

Nanoparticle and polysaccharide conjugate: a potential candidate vaccine to improve immunological stimuli.

Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response.

Abrus precatorius agglutinin-derived peptides induce ROS-dependent mitochondrial apoptosis through JNK and Akt/P38/P53 pathways in HeLa cells.

10kDAGP, a tryptic digest of Abrus precatorius lectin 'Agglutinin' is known to induce apoptosis by mitochondria-dependent pathways in human cervical cancer (HeLa) cells. The present study was focused on deciphering the detailed molecular mechanism of apoptosis induction in vitro by 10kDAGP and also its in vivo therapeutic efficacy. For in vivo model, HeLa cell encapsulated hollow fiber was implanted in Swiss Albino mice and treated with 10kDAGP. Our results showed that 10kDAGP was able to enter the cell within a span of 20min and co-localized with mitochondria after 90min. of incubation. A drastic loss of mitochondrial membrane potential was noted within 6h of 10kDAGP administration along with an increase in ROS generation. ROS further led to symptoms of early apoptosis by deregulating Akt (Protein Kinase B) and activating c-Jun N-terminal Kinase (JNK), p38 Mitogen Activated Protein Kinase (MAPK), p53, and autophagy starting from ∼8h of incubation. Besides in vitro conditions, 10kDAGP activated JNK to mediate cancer cell killing in vivo. Therefore, 10kDAGP can be an excellent therapeutic agent as it can act through different ways in the cellular system. Future studies are directed to screen out active peptides from the pool of peptides and to study whether the mode of action is in synergistic way or in individual forms.

Antitumor effect of soybean lectin mediated through reactive oxygen species-dependent pathway.

AIMS: The present study evaluated the potential role of soybean lectin's (SBL) anticancer effect in vitro in different cancer cell lines and the therapeutic effectiveness in vivo in Dalton's lymphoma (DL) bearing mice model. MAIN METHODS: The effect of SBL on cell growth and viability was measured using MTT assay in different cancer cells in vitro. Apoptosis, autophagic cell death, DNA-damaging potential and reactive oxygen species (ROS) were analyzed in HeLa cells. The in vivo efficacy of SBL was demonstrated in Dalton's lymphoma (DL) bearing mice. KEY FINDINGS: SBL demonstrated clear, strong antiproliferative activity without affecting normal cells; however, heat denaturation of SBL diminished the antiproliferative efficacy of molecule as demonstrated by MTT assay. A sharp 74.51 ± 3.5% and 82.95 ± 5.8% inhibition of tumor cell proliferation in DL mice occurred when SBL was administered at a dosage of 1 and 2mg/kg body weight (i.p.), respectively, for ten days with the induction of autophagic and apoptotic cell death. An in vitro investigation revealed that SBL-mediated autophagy, apoptosis and DNA damage in HeLa cells were inflicted through the generation of ROS in a dose-dependent manner. Interestingly, pre-treating HeLa cells with N-acetylcysteine (NAC), a typical ROS scavenger, led to a noticeable reduction in SBL-induced autophagy, apoptosis and DNA-damaging activities, suggesting that SBL's antitumor potential was governed by ROS activation. SIGNIFICANCE: In this study, we evaluated the apoptotic, autophagic death, and DNA-damaging effects of SBL in cancer cells, which may have the potential to be used as a phyto-derived protein for cancer therapy.

A partially methylated mannogalactan from hybrid mushroom pfle 1p: purification, structural characterization, and study of immunoactivation.

A new water-soluble heteropolysaccharide (PS-II) with apparent molecular weight ∼1.65×10(5) Da, was isolated from the fruiting bodies of hybrid mushroom pfle 1p by hot aqueous extraction. It is composed of d-mannose, d-galactose, and 3-O-Me-d-galactose in a molar ratio of 1.0:0.99:1.1. The structural investigation of PS-II has been carried out using acid hydrolysis, methylation analysis, periodate oxidation study, and 1D/2D NMR experiments. Based on the results of these experiments, it was established that PS-II contained a main chain of (1→6) linked α-d-galactopyranosyl residues, one of which was substituted at C-2 by a terminal mannopyranosyl residue and also methylated at C-3 position. This heteropolysaccharide (PS-II) exhibited macrophage activation by NO production as well as in vitro splenocyte and thymocyte stimulation.

Biochemical analysis and antitumour effect of Abrus precatorius agglutinin derived peptides in Ehrlich's ascites and B16 melanoma mice tumour model.

Anticancer and immunostimulatory properties of tryptic digest peptides of Abrus precatorius agglutinin protein (10kDAGP) have already been reported. Here attempt has been made to further validate anticancer properties of 10kDAGP peptides in Ehrlich's ascites carcinoma (EAC) and B16 melanoma (B16M) bearing mice models and to analyze 10kDAGP by anion exchange chromatography and RP-HPLC for obtaining the bioactive fraction from the total peptide pool. 10kDAGP treatment decreased the tumour pack volume by ∼82% for EAC and 58.8% for B16M. It also showed increase in ex vivo proliferation of splenocyte and thymocyte isolated from tumour bearing mice and increase in TNF-α and Interferon-γ in splenocyte culture supernatant. From chromatographic analysis it was found that anionic peptide fraction may be responsible for anti-proliferative activities of 10kDAGP. As most anticancer peptides are cationic in nature, further studies regarding bioactivity of anionic peptide fraction may lead to novel anticancer peptides and pathways of action.

Heteroglucan-dendrimer glycoconjugate: a modulated construct with augmented immune responses and signaling phenomena.

BACKGROUND: Newer strategies for augmenting immune responses of pharmacologically active glucans may serve to improve the medicinal potential of these biomolecules. With this aim, the present work was focused on generating targeted high molecular size glucan particles with magnified immune response activity. METHODS: Heteroglucans were conjugated with PAMAM dendrimers using a Schiff base reductive amination reaction to generate a polytethered molecule with multiple glucan motifs. The modulated construct was characterized by FTIR, TEM, (1)H NMR and dynamic light scattering (DLS) methods. Effects of conjugated glucans were examined in RAW 264.7 macrophage cells as well as in S-180 murine tumor models. RESULTS: Dendrimer-conjugated glucans were found to exhibit a two-fold increase in immune stimulation in comparison to unconjugated glucans. This may be corroborated by the predominant enhancement in immunological functions such as nitric oxide production, ROS generation and immune directed tumor inhibition in murine models. Immune cell surface markers (CD4, CD8, CD19, MHC-II) and cytokine levels were also found to be highly up-regulated in the splenocytes of mice subjected to particulate glucan administration. Our study also demonstrated that conjugated glucan treatment to RAW 264.7 cells strongly enhanced the phosphorylation of two downstream signalling molecules of the mitogen activated protein kinase (MAPKs) family: p38 and MEK1/2 relative to single glucans thereby relating molecular mechanisms with enhanced immune stimulation. CONCLUSIONS AND GENERAL SIGNIFICANCE: The results obtained thus support that particulate format of soluble heteroglucan will thereby improve its functionality and identify leads in therapeutic competence.

Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death.

AIM: Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS: Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice. RESULTS: AGG induced apoptosis in HepG2 cells in a dose- and time-dependent manner. AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9 activities and a sharp decrease in the Bcl-2/Bax ratio, indicating activation of a caspase cascade. Co-treatment of HepG2 cells with AGG and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells decreased the caspase 3/7 activity in comparison to HepG2 cells exposed only to AGG. Moreover, AGG decreased the expression of Hsp90 and suppressed Akt phosphorylation and NF-κB expression in HepG2 cells. Finally, AGG treatment significantly reduced tumor growth in nude mice bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31 and Ki-67 expression compared to levels observed in the untreated control mice bearing HepG2 cells. CONCLUSION: AGG inhibits the growth and progression of HepG2 cells by inducing caspase-mediated cell death. The agglutinin could be an alternative natural remedy for the treatment of human hepatocellular carcinomas.

Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced autophagy in HeLa cells.

Concanavalin A (Con A), a mannose or glucose specific legume lectin, is well known for its anti-proliferative and cytotoxic effect on different types of cancer cells, through its binding to the membrane receptors leading to a major stimulus for the induction of distinct metabolic responses. Recently it has been also been proved that, Con A induces autophagy in hepatoma cells through internalization and mitochondria mediated pathway involving a mitochondrial interacting protein named Bcl2/E1B-19kDa protein-interacting protein 3 (BNIP3). Through this current endeavor, we propose a membrane associated pathway involved in Con A induced autophagy, taking Human cervical cancer (HeLa) cell as a cancer model. Here, we deciphered the role of membrane mediated phosphatidylinositol 3 kinase (PI3K)/Akt/mTOR (mammalian target of rapamycin) and MEK/Extracellular signal-regulated kinases (ERK) pathway in Con A induced autophagy in HeLa cells. Subsequently, we found that Con A treatment suppresses the PI3K/Akt/mTOR and up regulates the MEK/ERK pathway leading to the activation of autophagy. This study will further help us to understand the mechanism behind the autophagic pathway induced by Con A and simultaneously it will strengthen its effective use as a prospective cancer chemo-therapeutic.

Prediction and validation of apoptosis through cytochrome P450 activation by benzo[a]pyrene.

Polycyclic aromatic hydrocarbons (PAHs) processed by cytochrome P450 (CYP450) during metabolism is well reported to induce carcinogenesis. The present study has developed a new approach to examine apoptotic activity of a known PAH called benzo[a]pyrene (B[a]P), using protein-ligand and protein-protein interaction through in silico approach, followed by in vitro validation. In silico study showed that the conformational changes and energies involved in the binding of B[a]P to CYP1B1 was crucial with its target proteins. The data showed that activated B[a]P had high affinity to bind with aryl hydrocarbon receptor (AhR) with binding energy of -601.97kcal/mol. Interestingly, B[a]P-CYP1B1 complex showed strong binding affinity for caspase-8, -9, -3 with binding energy of -625.5, -479.3 and -514.2kcal/mol respectively. Moreover, the docking of specific caspase inhibitors in the complex showed weak interaction with low binding energy value as compared to B[a]P-CYP1B1 caspase complexes. To validate our in silico work, we showed B[a]P treated HaCaT cells triggered apoptosis with increase in caspase 8, caspase 9 and caspase 3/7 level. Further, in vitro work confirmed that B[a]P induced apoptosis was significantly suppressed in Ac-DEVD-CMK pre-treated cells. In addition, knockdown of CYP1B1 suppressed B[a]P induced apoptosis in HaCaT cells confirming a pivotal role of CYP1B1 in B[a]P induced apoptosis. Interestingly, through in silico modeling, we screened clotrimazole as a potent CYP1B1 inhibitor which completely inhibited B[a]P mediated activation. This hypothesis was validated by MTT assay, caspase activation measurement and showed remarkable inhibition of B[a]P induced cell death; thereby, highlighting a potent therapeutic role for industrial pollution associated diseases.

Structural and immunological studies of an exopolysaccharide from Acinetobacter junii BB1A.

A water-soluble heteropolysaccharide (PS) was isolated from extracellular polymeric substances (EPS) produced by a novel metal tolerant bacterium, Acinetobacter junii BB1A. Sugar analysis showed that the PS was composed of mannose, galactose and arabinose in a molar ratio of nearly 3:1:1. Structural characterization of the PS was carried out using methylation analysis, periodate oxidation, Smith degradation and 1D/2D NMR experiments. Methylation analysis revealed that the PS was consisted of 2,4-linked-mannopyranosyl, 3,4-linked-mannopyranosyl, 2-linked-galactopyranosyl, terminal mannopyranosyl and arabinopyranosyl residues in a relative proportion of nearly 1:1:1:1:1. Smith degradation of the PS showed the presence of hydrated glyceraldehyde containing disaccharide unit consisting of α-d-Manp-(1→and→4)-α-d-Manp-(1→residues where the later was directly attached to a hydrated glyceraldehyde moiety. This polysaccharide showed significant in vitro splenocyte, thymocyte, and macrophage activations with optimum dose of 100 µg/mL for macrophage and 25 µg/mL both for the splenocyte and thymocyte.

In vitro and in vivo antitumor effects of Peanut agglutinin through induction of apoptotic and autophagic cell death.

In this study we unravel the mechanism underlying the antitumorigenic effects of Peanut agglutinin (PNA) isolated from Arachis hypogea in Dalton's lymphoma (DL) bearing mice and elucidated the mechanism in vitro in HeLa cells. In vivo PNA administration at 1 and 2 mg/kg body weight reduced DL proliferation with increase in autophagic and apoptotic characteristics. In vitro data showed that PNA at 0.1-100 µg/ml dose exhibit selective antiproliferative activity on various cancer cell lines without displaying cytotoxic effect on normal cells. However, heat denatured PNA failed to show any antiproliferative activity. Moreover, PNA was found to induce autophagic and apoptotic cell death in HeLa cells. Exponential increase in reactive oxygen species (ROS) was proved to be the master signal for promoting PNA induced cell death in HeLa cells. Interestingly, when HeLa cells were pre-exposed with N-acetylcysteine (NAC) and followed to PNA treatment, there was sharp decline in autophagy, apoptosis and a concomitant abrogation of antiproliferative potential. PNA at lower doses was also seen to inflict senescence. Hence, this common culinary item derived molecule whose discovery dates back to late 1970s was for the first time evaluated mechanistically in vivo and in vitro as a novel naturally occurring therapeutic agent against cancer.