Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl-xL, caspase-3/9, and oxidative stress modulators in HepG2 cell line.

Cucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti-inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl-2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl-xL, caspase-3, and caspase-9. We evaluated the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose-dependent manner. The cucurbitacins induced apoptosis by increasing caspase-3, caspase-9, and Bax activity, inhibiting Bcl-xL activation, causing loss of ΔΨm, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl-xL, caspase-3/9 signaling, and causing intracellular ROS increase in HepG2 cells.

Squirting Cucumber, Ecballium elaterium (L.) A. Ritch: An Update of Its Chemical and Pharmacological Profile.

Ecballium elaterium, also known as squirting cucumber, is a plant which is widespread in temperate regions of Europe, Africa and Asia. The plant is considered to be one of the oldest used drugs. In the last decades, E. elaterium has been widely studied as a source of triterpene metabolites named cucurbitacins, often found as glycosylated derivatives, used by the plant as defensive agents. Such metabolites exhibit several biological activities, including cytotoxic, anti-inflammatory, and anti-cancer. Interestingly, the bioactive properties of E. elaterium extracts have been investigated in dozens of studies, especially by testing the apolar fractions, including the essential oils, extracted from leaves and fruits. The purpose of this review is to provide an overview of the chemical profile of different parts of the plants (leaves, flowers, and seeds) analyzing the methods used for structure elucidation and identification of single metabolites. The pharmacological studies on the isolated compounds are also reported, to highlight their potential as good candidates for drug discovery.

Chinese herb related molecules Catechins, Caudatin and Cucurbitacin-I inhibit the proliferation of glioblastoma by activating KDELR2-mediated endoplasmic reticulum stress.

Brain gliomas are difficult in the field of tumor therapy because of their high recurrence rate, high mortality rate, and low selectivity of therapeutic agents. The efficacy of Traditional Chinese Medicine (TCM) in the treatment for tumours has been widely recognized. Here, three Chinese herb related molecules, namely Catechins, Caudatin and Cucurbitacin-I, were screened by bioinformatic means, and were found to inhibit the proliferation of glioblastoma T98G cells using Colony-forming and CCK-8 assays. Notably, the simultaneous use of all three molecules could more significantly inhibit the proliferation of glioma cells. Consistent with this, temozolomide, each in the combination with three molecules, could synergistically inhibit the proliferation of T98G cells. Results of qPCR assay was also showed that this inhibition was through the activation of the KDELR2-mediated endoplasmic reticulum stress (ER) pathway. Molecular docking experiments further revealed that Catechins, Caudatin and Cucurbitacin-I could activate ER stress might by targeting KDELR2. Taken together, these results suggest that these herbal molecules have the potential to inhibit the growth of glioma cells and could provide a reference for clinical therapeutic drug selection.

Cucurbitacin B: A review of its pharmacology, toxicity, and pharmacokinetics.

Cucurbitacin B (CuB, C32H46O8), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.

Cucurbitacin mediated regulation of deregulated oncogenic signaling cascades and non-coding RNAs in different cancers: Spotlight on JAK/STAT, Wnt/ß-catenin, mTOR, TRAIL-mediated pathways.

Research over decades has enabled us in developing a better understanding of the multifaceted and heterogeneous nature of cancer. High-throughput technologies have helped the researchers in unraveling of the underlying mechanisms which centrally regulate cancer onset, metastasis and drug resistance. Our rapidly expanding knowledge about signal transduction cascade has added another layer of complexity to already complicated nature of cancer. Deregulation of cell signaling pathways played a linchpin role in carcinogenesis and metastasis. Cucurbitacins have gained tremendous attention because of their remarkable pharmacological properties and considerable ability to mechanistically modulate myriad of cell signaling pathways in different cancers. In this review, we have attempted to provide a mechanistic and comprehensive analysis of regulation of oncogenic pathways by cucurbitacins in different cancers. We have partitioned this review into separate sections for exclusive analysis of each signaling pathway and critical assessment of the knowledge gaps. In this review, we will summarize most recent and landmark developments related to regulation of Wnt/ß-catenin, JAK/STAT, mTOR, VEGFR, EGFR and Hippo pathway by cucurbitacins. Moreover, we will also address how cucurbitacins regulate DNA damage repair pathway and TRAIL-driven signaling in various cancers. However, there are still outstanding questions related to regulation of SHH/GLI, TGF/SMAD and Notch-driven pathway by cucurbitacins in different cancers. Future studies must converge on the analysis of full-fledge potential of cucurbitacins by in-depth analysis of these pathways and how these pathways can be therapeutically targeted by cucurbitacins.

Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms.

Since ancient times, plants have been an extensive reservoir of bioactive compounds with therapeutic interest for new drug development and clinical application. Cucurbitacins are a compelling example of these drug leads, primarily present in the plant kingdom, especially in the Cucurbitaceae family. However, these natural compounds are also known in several genera within other plant families. Beyond the Cucurbitaceae family, they are also present in other plant families, as well as in some fungi and one shell-less marine mollusc. Despite the natural abundance of cucurbitacins in different natural species, their obtaining and isolation is limited, as a result, an increase in their chemical synthesis has been developed by researchers. Data on cucurbitacins and their anticancer activities were collected from databases such as PubMed/MedLine, TRIP database, Web of Science, Google Scholar, and ScienceDirect and the information was arranged sequentially for a better understanding of the antitumor potential. The results of the studies showed that cucurbitacins have significant biological activities, such as anti-inflammatory, antioxidant, antimalarial, antimicrobial, hepatoprotective and antitumor potential. In conclusion, there are several studies, both in vitro and in vivo reporting this important anticancer/chemopreventive potential; hence a comprehensive review on this topic is recommended for future clinical research.

Cucurbitacin IIa: A review of phytochemistry and pharmacology.

Cucurbitacin IIa was first found in plants and it belongs to tetracyclo triterpenoids. It is one of the most important active components in cucurbitaceae plants. Studies have found that cucurbitacin IIa has a variety of pharmacological effects, such as antitumor, antiinflammatory, antibacterial, antihepatitis B virus, inhibition of human immunodeficiency virus replication, and antidepressant effect. However, the underlying mechanisms, intracellular targets, and structure-activity relationships of cucurbitacin IIa remain to be completely elucidated. This review summarizes the current advances concerning the phytochemistry and pharmacology of cucurbitacin IIa. Electronic databases such as PubMed, Web of Science, Google Scholar, Science Direct, and CNKI were used to find relevant information about cucurbitacin IIa using keywords such as "Cucurbitacin IIa," "Pharmacology," and "Phytochemistry." These pharmacological effects involve the actin cytoskeleton aggregation, the regulation of JAK2/STAT3, ERBB-MAPK, CaMKII α/CREB/BDNF signal pathways, as well as the regulation of survivin, caspases, and other cell cycles, apoptosis, autophagy-related cytokines, and kinases. It has high development and use value.

Suppressive Effect of Two Cucurbitane-Type Triterpenoids from Momordica charantia on Cutibacterium acnes-Induced Inflammatory Responses in Human THP-1 Monocytic Cell and Mouse Models.

Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5ß,19-epoxycucurbita-6,23-dien-3ß,19,25-triol (Kuguacin R; KR) and 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1ß, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1ß-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.

Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives.

In the ongoing efforts to discover natural cholesterol-lowering compounds, dihydrocucurbitacin B, isolated from Trichosanthes cucumeroides roots, was found to promote LDL uptake by upregulating LDLR protein in a PCSK9-dependent process. In this study, an in-depth investigation of T. cucumeroides roots afforded 27 cucurbitacins (1-27), including seven new cucurbitacins (1-7), and their structures were elucidated by spectroscopic data analyses. In order to gain insight into their structure-activity relationship, cucurbitacin derivatives (B1-11 and DB1-11) were synthesized. Evaluation of lipid-lowering activities of these cucurbitacins by an LDL uptake assay in HepG2 cells revealed that most of the compounds improved the LDL uptake rate, among which hexanorisocucurbitacin D (6) and isocucurbitacin D (21) exhibited the highest activities (rates of 2.53 and 2.47, respectively), which were comparable to that of the positive control, nagilactone B (rate of 2.07). According to a mechanistic study by Western blot analysis, compounds 6 and 21 dose-dependently increased LDLR protein levels and reduced PCSK9 protein levels, representing promising new lipid-lowering drug candidates.

Effect of Ginsenoside-Rh2 and Curcurbitacin-B on Cryptosporidium parvum in vitro.

Ginsenoside-Rh2 and cucurbitacin-B (CuB) are secondary metabolites of Ginseng (Panax ginseng) and Cucurbitaceae plants respectively. We assessed the anticryptosporidial activity of these two functional compounds in a cell culture model of cryptosporidiosis. The highest concentration of each compound that was not toxic to the host cells was used to assess the activity against C. parvum during infection/invasion and growth in HCT-8 cell monolayers. Monolayers were infected with pre-excysted C. parvum oocysts. Infected monolayers were incubated at 37 °C for 24 h and 48 h in the presence of different concentrations of each test compound. A growth resumption assay was performed by incubating infected monolayers in the presence of compounds for 24 h followed by a second 24-h incubation in the absence of compound. To screen for invasion inhibiting activity, freshly excysted C. parvum sporozoites were pre-treated with different concentrations of compounds prior to adding them to the cell monolayers. Paromomycin, a known inhibitor of C. parvum, and DMSO were used as positive and negative control, respectively. The level of infection was initially assessed using an immunofluorescent assay and quantified by real-time PCR. Both compounds were found to strongly inhibit C. parvum intracellular development in a dose-dependent manner. IC50 values of 25 µM for a 24 h development period and 5.52 µM after 48 h development were measured for Rh2, whereas for CuB an IC50 value of 0.169 µg/ml and 0.118 µg/ml were obtained for the same incubation periods. CuB also effectively inhibited resumption of growth, an activity that was not observed with Rh2. CuB was more effective at inhibiting excystation and/or host cell invasion, indicating that this compound also targets extracellular stages of the parasite.

Design, synthesis and biological study of hybrid drug candidates of nitric oxide releasing cucurbitacin-inspired estrone analogs for treatment of hepatocellular carcinoma.

Development of hybrid drug candidates is well known strategy for designing antitumor agents. Herein, a novel class of nitric oxide donating cucurbitacin inspired estrone analogs (NO-CIEAs) were designed and synthesized as multitarget agents. Synthesized analogs were initially evaluated for their anti-hepatocellular carcinoma activities. Among the tested analogs, NO-CIEAs 17 and 20a exhibited more potent activity against HepG2 cells (IC50 = 4.69 and 12.5 µM, respectively) than the reference drug Erlotinib (IC50 = 25 µM). Interestingly, NO-CIEA 17 exerted also a high potent activity against Erlotinib-resistant HepG2 cell line (HepG2-R) (IC50 = 8.21 µM) giving insight about its importance in drug resistance therapy. Intracellular measurements of NO revealed that NO-CIEAs 17 and 20a showed a significant increase in NO production in tumor cells after 1 h of incubation comparable to the reference prodrug JS-K. Flow cytometric analysis showed that both NO-CIEAs 17 and 20a mainly arrested the HepG2 cells in the G0/G1 phase. Also, In-Cell Based ELISA screening showed that NO-CIEA 17 resulted in a potential inhibitory activity towards the EGFR and MAPK (25% and 29% inhibition compared to untreated control cells, respectively). This data suggests the binding ability of NO-CIEA 17 to the EGFR and ERK to be well correlated along with the docking and cellular studies. Also, treatment of HepG2-R cells with NO-CIEA 17 showed a potential reduction of MRP2 expression in a dose dependent manner providing a significant impact on the chemotherapeutic resistance. Overall, the current study provides a potential new approach for the discovery of a novel antitumor agent against HCC.

Cucurbits Plants: A Key Emphasis to Its Pharmacological Potential.

Cucurbita genus has received a renowned interest in the last years. This plant species, native to the Americas, has served worldwide folk medicine for treating gastrointestinal diseases and intestinal parasites, among other clinical conditions. These pharmacological effects have been increasingly correlated with their nutritional and phytochemical composition. Among those chemical constituents, carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, and functional carbohydrates and polysaccharides are those occurring in higher abundance. However, more recently, a huge interest in a class of triterpenoids, cucurbitacins, has been stated, given its renowned biological attributes. In this sense, the present review aims to provide a detailed overview to the folk medicinal uses of Cucurbita plants, and even an in-depth insight on the latest advances with regards to its antimicrobial, antioxidant and anticancer effects. A special emphasis was also given to its clinical effectiveness in humans, specifically in blood glucose levels control in diabetic patients and pharmacotherapeutic effects in low urinary tract diseases.

Isolation of anticancer constituents from Cucumis prophetarum var. prophetarum through bioassay-guided fractionation.

BACKGROUND: Cucumis prophetarum var. prophetarum is used in Saudi folk medicine for treating liver disorders and grows widely between Abha and Khamis Mushait City, Saudi Arabia. METHODS: Bioassay-guided fractionation and purification were used to isolate the main active constituents of Cucumis prophetarum var. prophetarum fruits. These compounds were structurally elucidated using NMR spectroscopy, mass spectral analyses and x-ray crystallography. All fractions, sub-fractions and pure compounds were screened for their anticancer activity against six cancer cell lines. RESULTS: The greatest cytotoxic activity was found to be in the ethyl acetate fraction, resulting in the isolation of five cucurbitacin compounds [E, B, D, F-25 acetate and Hexanorcucurbitacin D]. Among the cucurbitacins that were isolated and tested cucurbitacin B and E showed potent cytotoxicity activities against all six human cancer cell lines. CONCLUSION: Human breast cancer cell lines were found to be the most sensitive to cucurbitacins. Preliminary structure activity relationship (SAR) for cytotoxic activity of Cucurbitacins against human breast cancer cell line MDA-MB-231 has been reported.

Anticancer activity of cucurbitacin-A in ovarian cancer cell line SKOV3 involves cell cycle arrest, apoptosis and inhibition of mTOR/PI3K/Akt signaling pathway.

PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation. DAPI staining using fluorescence microscopy was used to evaluate the effects of the compound on apoptosis. Flow cytometry was used to study the effects on cell cycle phase distribution, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) loss. RESULTS: Cucurbitacin-A exhibited an IC50 of 40 µM against ovarian SKVO3 cancer cell line. It also caused DNA damage in SKVO3 cells and also prompted ROS mediated alterations in MMP. On the other hand, it triggered cell cycle arrest of SKVO3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that cucurbitacin-A considerably inhibited the expression levels of key proteins of PI3K/Akt/ mTOR signaling pathway. CONCLUSION: The study showed that cucurbitacin-A is a potent agent against ovarian cancer cells, can be considered for further in vivo research and can also be developed as a possible lead molecule.

Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549.

Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential.

Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin 15 activated dendritic cell against lymphoma and leukemia via TRAIL.

Effector functions in tumor resistance by dendritic cells (DCs) are less well characterized. In this study, we describe that the murine DCs upon stimulation with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact tumor cells significantly reduces the DC mediated tumoricidal effect, possibly via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived TRAIL was further augmented by deactivation of STAT3 in tumor cells by cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition to activation of caspases. Compared to naïve DCs, DCs from tumor bearing mice are significantly impaired in TRAIL expression and consequent antitumor functions against DL which was partially restored by activation with IL-15 or LPS. Priming with recombinant IL-15 prolongs the survival of tumor bearing mice treated with cucurbitacin I. Naïve peripheral blood DCs derived from chronic myeloid leukemia (CML) patients have significant impairment in expression of TRAIL and consequent tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary tumor cells compared to normal control.

The antigluconeogenic activity of cucurbitacins from Momordica charantia.

Five new cucurbitacins, kuguacins II-VI (1-5), along with five known analogues (6-10), were obtained from the fruit of Momordica charantia. Structures of the new compounds were elucidated as 5ß,19-epoxycucurbit-23-en-7-on-3ß,25-diol (1), 5ß,19-epoxycucurbit-7,23-dion-3ß,25-diol (2), 5ß,19-epoxycucurbit-6-en-19,23-dion-3ß,25-diol (3), 5ß,19-epoxy-23,24,25,26,27-pentanorcucurbit-6-en-7,19-dion-3ß,22-diol (4), and cucurbit-5-en-7,23-dion-3ß,19,25-triol (5) by extensive spectroscopic and single-crystal X-ray diffraction analyses. Some cucurbitane compounds from this species were screened for their potential antidiabetic properties in terms of antigluconeogenic activity. As a result, compounds 1, 10, 11, and 12 (at 25-100 µM) showed concentration-dependent inhibition on glucose production from liver cells. In addition, compounds 11 and 12 (at 100 µM) showed around 20-30 % inhibition on PEPCK activity.

A Review: Phytochemicals Targeting JAK/STAT Signaling and IDO Expression in Cancer.

Cancer remains a major health problem worldwide. Among many other factors, two regulatory defects that are present in most cancer cells are constitutive activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and the induction of indoleamine 2, 3-dioxygenase (IDO), an enzyme that catalyzes tryptophan degradation, through JAK/STAT signaling. Cytokine signaling activates STAT proteins in regulating cell proliferation, differentiation, and survival through modulation of target genes. Many phytochemicals can inhibit both JAK/STAT signaling and IDO expression in antigen-presenting cells by targeting different pathways. Some of the promising phytochemicals that are discussed in this review include resveratrol, cucurbitacin, curcumin, (-)-epigallocatechin gallate, and others. It is now evident that phytochemicals play key roles in inhibition of tumor proliferation and development and provide novel means for therapeutic targeting of cancer.

Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad.

Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro cytotoxic activity of the isolated compounds against two human colon cancer cell lines (HT29 and Caco-2) and one normal rat intestine epithelial cell line (IEC6), revealed that one of the isolated compounds presented interesting specific cytotoxic activity towards colorectal cell lines.

Cucurbitacins: potential candidates targeting mitogen-activated protein kinase pathway for treatment of melanoma.

Cucurbitacins (Cucs) have been classified as signal transducer and activator of transcription 3 inhibitors. Kinase inhibition has been a validated drug target in multiple types of malignancies. B-RAF mutations are highly expressed in the melanoma. Our hypothesis is the Cucs can be a potential candidate to inhibit the signaling kinase pathway. The research presented is the evaluation of Cucs, as B-RAF and MEK1 kinase inhibitors. Virtual screening methods were employed to identify lead compounds. The hypothesis was tested on mutant B-RAF cell lines, A-375 and Sk-Mel-28 cell lines to determine the activity toward melanoma. A series of natural Cucs show an improved activity toward Sk-Mel-28 and A-375 cell lines. Cucs show potential inhibition for the total and phosphorylated ERK using ELISA kits. Cucs could be potential candidate for inhibiting cell growth.