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Abstract Canolol (4-vinylsyringol), extracted form crude canola oil, is the promising drug toward cancer prevention and treatment. The current studies focus on the role of COX-2 signaling pathway in canolol-induced apoptosis in cancer cells. It is still unknown whether mitochondria and MAPK signaling pathways are involved. To elucidate the roles of above signaling pathways in canolol-induced apoptosis in cancer cells, human cervical carcinoma cell line HeLa and HeLa xenograft tumor model are adopted. Canolol induced apoptosis of HeLa cells and inhibited tumor growth with low systemic adverse effect, accompanying with excess generation of intracellular ROS and lysosome rupture. The results in vitro and in vivo confirmed that MAPK signaling pathways mediated mitochondrial signaling pathway activation were involved in canolol-induced apoptosis. In conclusion, these data showed that canolol induced apoptosis in HeLa cells through ROS-MAPK mediated mitochondrial signaling pathway, providing a view of the potential application of canolol as an anticancer agent. Highlights • Canolol inhibited cell survival and induced apoptosis in HeLa cells. • Canolol activated MAPK and mitochondrial signaling pathways in HeLa cells. • Canolol had less cytotoxicity in vitro and low systemic adverse effect in vivo. [ABSTRACT FROM AUTHOR]

The Journal of Biological Chemistry (JBC) has been a major vehicle for disseminating and recording the discovery and characterization of proteolytic enzymes. The pace of discovery in the protease field accelerated during the 1971-2010 period that Dr. Herb Tabor served as the JBC's editor-in-chief. When he began his tenure, the fine structure and kinetics of only a few proteases were known; now thousands of proteases have been characterized, and over 600 genes for proteases have been identified in the human genome. In this review, besides reflecting on Dr. Tabor's invaluable contributions to the JBC and the American Society for Biochemistry and Molecular Biology (ASBMB), I endeavor to provide an overview of the extensive history of protease research, highlighting a few discoveries and roles of proteases in vivo. In addition, metalloproteinases, particularly meprins of the astacin family, will be discussed with regard to structural characteristics, regulation, mechanisms of action, and roles in health and disease. Proteases and protein degradation play crucial roles in living systems, and I briefly address future directions in this highly diverse and thriving research area. [ABSTRACT FROM AUTHOR]

We investigated the effects of Stattic, an important signal transducer and activator of transcription 3 (STAT3) inhibitor, on enhancing the anti-proliferative and apoptotic effects of docetaxel in lung A549 and prostate cancer DU145 cells. Cell proliferation, cellular apoptosis and expression of STAT3 target genes were evaluated by DAPI staining, Annexin V/PI staining, cell cycle analysis and Real Time PCR. The anticancer effects of docetaxel and Stattic combination therapy induced synergistic effects in A549 and DU145 cells with combination indices of 0.71 and 0.52, respectively. Annexin V/PI demonstrated that there was a 2-fold increase in the proportion of apoptotic cells in cells treated with docetaxel and Stattic in A549 and DU145 cell lines, compared with control groups. Compared with cells treated with either docetaxel or Stattic alone, the results of the current study identified a significant decrease in the transcript levels of the anti-apoptotic proteins Bcl-2 and Bcl-xl and a marked increase in the level of the pro-apoptotic protein, Bax in cells that underwent combination therapy with docetaxel and Stattic combination (P < 0.05). These results suggest that combination of a STAT3 inhibitor and taxan derivatives may be developed as a promising therapeutic strategy to treat patients with lung and prostate cancer. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide due to its chemoresistance and poor prognosis. Currently, there is a lack of effective small molecule drugs for the treatment of ESCC. Microtubules are an attractive target for cancer therapy since they play a central role in various fundamental cell functions. We investigated the anti-ESCC activity and mechanisms of the small molecule tubulin ligands, SL-3-19 and SL-1-73, which are two carbazole sulfonamide derivatives, in vitro and in vivo for the first time. These drugs were previously screened from a small molecule library with over 450 compounds and optimized for high aqueous solubility [1,2]. Here, we reveal the promising activities of these compounds against esophageal cancer. Mechanistically, both SL-3-19 and SL-1-73 inhibited ESCC cell growth by inducing cell apoptosis and arresting the cell cycle at G2/M phase in a dose-dependent manner. These drugs effectively inhibited microtubule assembly, greatly disrupted microtubule maturation by down-regulating acetylated α-tubulin, and significantly disrupted the vascular structure by obstructing the formation of capillary-like tubes in vitro. Consistent with their in vitro activities, SL-3-19 and SL-1-73 inhibited the growth of ESCC xenografts and inhibited the microvessel density in vivo. In summary, SL-3-19 and SL-1-73 are novel microtubule-destabilizing agents that have a potential antitumor effect on ESCC both in vitro and in vivo, and SL-3-19 had a higher activity than SL-1-73, with a low IC50 value and an observable antitumor activity in vivo. These results indicate that SL-3-19 may be a new therapeutic candidate for ESCC treatment. [ABSTRACT FROM AUTHOR]

Although methylene blue (MB) has showed strong antioxidant effect, its effect related with heme oxygenase-1 (HO-1) is still unclear. Thus, we investigated the effects of MB on HO-1 protein content and enzyme activity, and its protective effect against hydrogen peroxide (H 2 O 2 )-induced oxidative damage in RAW264.7 macrophage. The cell viability and the release of lactate dehydrogenase of RAW264.7 were determined. The mitochondrial functions were valuated through these indexes: content of adenosine triphosphate, superoxide dismutase, concentration of reactive oxygen species and mitochondrial membrane potential. Meanwhile, high content screening tested generation of ROS, MMP and intracellular concentration of calcium ion. qRT-PCR valuated macrophage phenotype markers expression. Lastly, flow cytometry and caspase-3 detection analyzed RAW264.7 apoptosis. Our data showed that (1) Both pretreatment and posttreatment of MB increased HO-1 protein content and enzyme activity; (2) MB rescued cells from H 2 O 2 -induced mitochondrial dysfunction; (3) High content screening revealed that MB alleviated the changes including generation of reactive oxygen species, mitochondrial membrane potential and intracellular concentration of calcium ion in H 2 O 2 exposed RAW264.7; (4) MB attenuated H 2 O 2 -induced apoptosis; (5) MB pretreatment decreased the expression of M1 macrophage markers ( Tnf and Nos2 ) while increasing the expression of M2 macrophage markers ( Mrc1 and Il10 ); (6) The beneficial effect of MB was abolished by zinc protoporphyrin IX (HO-1 activity inhibitor) or HO-1 siRNA. In summary, MB protects RAW264.7 cells from H2O2-induced injury through up-regulation HO-1. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3- d ]pyrimidine nucleoside; compounds 5 , and 6 . In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21 Cip1 protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaP C4-2 (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 μM compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21 Cip1 , which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21 Cip1 achieved in LNCaP C4-2 cells was possible by intensive cell treatment with compound 5 (9 μM, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 μM compound 5 -treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21 Cip1 nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells. [ABSTRACT FROM AUTHOR]

A novel cyclometalated iridium(III) complex, [Ir(CˆN) 2 (HPIP)]Cl (IrC) was synthesized and characterized. IrC exhibited about 10-fold higher cytotoxicity than cisplatin against A549 cancer cell line. Interestingly, a cisplatin-resistant cell line, A549-CP/R showed sensitivity to IrC. Further study suggested that IrC induced apoptosis via negatively regulated the nuclear factor-kappa B (NF-κB) pathway, which involved reactive oxygen species (ROS) generation, Bcl-2 and caspase family members activation. Taken together, these results suggest that IrC is able to overcome chemoresistance and may be an effective treatment for platinum-resistant cancer therapy. [ABSTRACT FROM AUTHOR]

Xanthohumol (XN), a prenylflavonoid derived from the hop plant ( Humulus lupulus L.) has been found to exhibit a broad spectrum of biological properties, including anti-cancer activity. In this study, the mechanisms involved in anti-cancer activity of XN in human RK33 and RK45 larynx cancer cell lines were investigated. The effect of XN on the viability of larynx cancer and normal cells (human skin fibroblasts HSF and rat oligodendroglia-derived cells, OLN-93) was compared. Additionally, the influence of XN on proliferation, cell cycle progression, induction of apoptosis in larynx cancer cells, as well as the molecular mechanisms underlying in these processes were analyzed. XN promoted the reduction of cell viability in cancer cells, but showed low cytotoxicity to normal cells. The decrease in cell viability in the cancer cells was coupled with induction of apoptosis via two pathways. The mechanisms involved in these effects of XN were associated with cell growth inhibition by induction of cell cycle arrest in the G 1 phase, increased p53 and p21/WAF1 expression levels, downregulation of cyclin D1 and Bcl-2, and activation of caspases-9, -8, and -3. Moreover, this compound inhibited phosphorylation of ERK1/2, suggesting a key role of the ERKs pathway in the XN-mediated growth suppressing effects against the studied cells. These results indicate that XN could be used as a potential agent for the treatment of patients with larynx cancer. [ABSTRACT FROM AUTHOR]

Ganoderic acids (GAs) produced by Ganoderma lucidum possess anticancer activities with the generation of reactive oxygen species (ROS). However, the role of oxidative stress in apoptotic process induced by GAs is still undefined. In this study, the effects of four structurally related GAs, i.e. GA-T, GA-Mk, and two deacetylated derivatives of GA-T (GA-T1 and GA-T2) on the antioxidant defense system and induced apoptosis in cervical cancer cells HeLa were investigated in vitro . Our results indicated that the tested GAs (5–40 μM) induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9 and caspase-3. Furthermore, GAs increased the generation of intracellular ROS and attenuated antioxidant defense system by decreasing glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The above effects were remarkably blocked by the exogenous antioxidants, i.e. N -acetylcysteine, catalase and diphenyleneiodonium chloride. The potency of the four GAs toward induced apoptosis, generation of ROS and suppression of antioxidant defense system was in the order of: GA-T > GA-Mk ≈ GA-T1 > GA-T2 in HeLa cells. These findings suggest that GAs induced mitochondria-dependent cell apoptosis in HeLa cells are mediated via enhancing oxidative stress and depressing antioxidant defense. Additionally, the acetylation of hydroxyl groups in GAs may contribute to their pro-oxidant activities and cytotoxicity, which is helpful to the development of novel chemotherapy agents. [ABSTRACT FROM AUTHOR]

Abstract: Chrysin exists widely in plants, honey and propolis. The anti-cancer property of chrysin has been demonstrated though the molecular mechanism is not clear. In this study, we found that pre-treatment with chrysin could promote the cell death induced by TRAIL according to the morphological changes and appearance of sub-G1 peak in four human cancer cell lines. In HCT-116 cells, the results of flow cytometry analysis showed that the percentage of sub-G1 reached (38.89±3.78) % when pre-treatment of chrysin was used at 40μM, but that was only (2.53±0.10) % in the untreated group and (13.22±0.20) % in TRAIL alone group. The differences between the combination and the untreated or TRAIL alone group were all significant (P <0.05) and dose-dependent effect was obvious. Similar results were obtained in CNE1 cells. In the search of molecular mechanisms, we found that pre-treatment with chrysin could increase TRAIL-induced degradation of caspase 3, caspase 8, PARP proteins. Z-VAD-fmk, which is a pan-caspase inhibitor, could inhibit the apoptosis enhanced by the combination of chrysin and TRAIL. All data indicate that chrysin can enhance the apoptosis induced by TRAIL, and the apoptosis is caspase-dependent and related to the activation of caspase 8. [Copyright &y& Elsevier]

Abstract: 2(±)-7,8,3′,4′,5′-pentamethoxyflavan (PMF), a synthetic flavan racemate, showed growth inhibitory effect on various kinds of tumor cells. The present study is to investigate the molecular mechanisms of action of PMF in human leukemia HL60 cells. Anti-proliferative effect of PMF on HL60 cells was associated with G2/M cell cycle arrest, which was mediated by regulating the expression of Cdc25C, cyclin A and p21 proteins and inhibiting the phosphorylation of Cdc2 at Thr161. PMF also induced apoptosis of HL60 cells via death receptor and mitochondria apoptotic pathways, which was characterized by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase, caspase-3, caspase-8 and caspase-9, changes of Bcl-2 and Bax expression, cytochrome c release from mitochondria and a decrease in the mitochondrial membrane potential (MMP). These data suggest that PMF produces anti-tumor effect via induction of G2/M cell cycle arrest and apoptosis. [Copyright &y& Elsevier]

Abstract: Inhibitory effects of geometrical isomers of fucoxanthin – characteristic carotenoid of brown seaweeds – on the growth of various cancer cells and on human leukemia (HL-60), colon cancer (Caco-2) and prostate cancer cells (PC-3 and LNCap) were comparatively evaluated. All-trans fucoxanthin was the major geometrical isomer (∼88%) found in the fresh brown seaweed (Undaria pinnatifida) apart from a small amount of 13-cis and 13′-cis isomers (∼9%). Incubation of the fucoxanthin isomeric mixtures, all-trans fucoxanthin with a small amount of 13-cis and 13′-cis isomers, produced 9′-cis isomer (5%) and increased the contents of 13-cis and 13′-cis isomers (27%). The antiproliferative effect of the mixture of 13-cis and 13′-cis isomers was stronger than all other geometrical isomers evaluated in the study. The inhibition of growth of HL-60 cells was higher in case of 13′-cis isomer followed by 13-cis and all-trans isomers. The potent inhibitory effect of 13-cis and 13′-cis fucoxanthin on HL-60 cells and Caco-2 cells could possibly be due to their higher apoptosis-inducing activity. [Copyright &y& Elsevier]

The essential hallmarks of cancer are intertwined with an altered cancer cell-intrinsic metabolism, either as a consequence or as a cause. As an example, the resistance of cancer mitochondria against apoptosis-associated permeabilization and the altered contribution of these organelles to metabolism are closely related. Similarly, the constitutive activation of signaling cascades that stimulate cell growth has a profound impact on anabolic metabolism. Here, we review the peculiarities of tumor cell metabolism that might be taken advantage of for cancer treatment. Specifically, we discuss the alterations in signal transduction pathways and/or enzymatic machineries that account for metabolic reprogramming of transformed cells. [Copyright &y& Elsevier]

Abstract: A systematic study was designed to elucidate differences in cytostatic activity in vitro between HPMA-based doxorubicin conjugates synthesized using different polymerization techniques and differing in peptidyl side chain. A polymer–drug conjugate containing doxorubicin (DOX) bound to HPMA copolymer backbone through the enzymaticaly non-cleavable sequence GlyGly shows low but significant cytotoxicity in vitro in seven cancer cell lines of mouse (EL4, 38C13, 3T3, BCL1) and human (SW620, Raji, Jurkat) origin. The low cytotoxicity can be considerably increased by the presence of additional drug-free GlyPheLeuGly side chains. P1 conjugate, i.e. non-targeted HPMA copolymer bearing doxorubicin bound via a biodegradable GlyPheLeuGly sequence, synthesized by direct copolymerization of HPMA with monomeric doxorubicin and thus without additional drug-free GlyPheLeuGly sequences is less effective compared to PK1 synthesized by polymer analogous reaction and thus containing extra drug-free GlyPheLeuGly sequences. Significant activity-enhancing effect was not seen with other amino acid/oligopeptide sequences (e.g., Gly or GlyGly). The activity-enhancing effect of GlyPheLeuGly sequences is more obvious in the conjugate containing doxorubicin bound to HPMA through GlyGly sequence. Derivatization of the terminal carboxyl group of the extra GlyPheLeuGly side chains (amide, N-substituted amide, free carboxyl) does not significantly influence the cytotoxicity of the conjugates. The presence of the GlyPheLeuGly sequence in the conjugate structure increases its rate of intracellular accumulation. Normal cells (Balb/c splenocytes) accumulate less polymer–doxorubicin conjugate compared to cancer cells (T cell lymphoma EL4, B cell lymphoma Raji and T cell leukemia JURKAT). [Copyright &y& Elsevier]

Summary: Cancer cells are typically characterized by increased resistance towards apoptosis. Livin (alternatively called ML-IAP or KIAP) is an anti-apoptotic protein which is expressed in several cancer forms. Using real-time reverse transcription-polymerase chain reaction (RT-PCR), we confirmed livin expression in a significant portion of non-small cell lung cancer (NSCLC) tissue samples and, in addition, detected livin expression in a number of NSCLC cell lines. In order to elucidate whether livin contributes to the apoptotic resistance of lung cancer cells, we silenced endogenous livin expression in a panel of cancer-derived NSCLC cell lines by RNA interference (RNAi). We observed that the targeted inhibition of livin strongly sensitized NSCLC cells to different pro-apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide. In addition, long-term silencing of livin blocked the outgrowth of NSCLC cells in colony formation assays. These effects of small interfering (si)RNA were specific for livin-expressing tumor cells. Our results indicate that Livin is an important contributor to the apoptosis resistance of NSCLC cells and may serve as a novel molecular target for therapeutic inhibition in NSCLC. [Copyright &y& Elsevier]

BAY 43-9006 is a kinase inhibitor that induces apoptosis in a variety of tumor cells. Here we report that treatment with BAY 43-9006 results in marked cytochrome c and AIF release into the cytosol, caspase-9, -8, -7, and -3 activation, and apoptosis in human leukemia cells (U937, Jurkat, and K562). Pronounced apoptosis was also observed in blasts from patients with acute myeloid leukemia. These events were accompanied by ERK1/2 inactivation and caspase-independent down-regulation of Mcl-1. Inducible expression of a constitutively active MEK1 construct did not prevent Mcl-1 down-regulation, suggesting that this event is not related to MEK/ERK pathway inactivation. Furthermore, BAY 43-9006 did not induce major changes in Mcl-1 mRNA levels monitored by real-time PCR or Mcl-1 promoter activity demonstrated by luciferase reporter assays, but it did enhance Mcl-1 down-regulation in actinomycin D-treated cells. Inhibition of protein synthesis by cycloheximide or proteasome function with MG132 and pulse-chase studies with [35S]methionine demonstrated that BAY 43–9006 did not diminish Mcl-1 protein stability, nor did it enhance Mcl-1 ubiquitination, but instead markedly attenuated Mcl-1 translation in association with the rapid and potent dephosphorylation of the elF4E translation initiation factor. Finally, ectopic expression of Mcl-1 in leukemic cells markedly inhibited BAY 43-9006-mediated cytochrome c cytosolic release, caspase-9, -7, and -3 activation, as well as cell death, indicating that Mcl-1 operates upstream of cytochrome c release and caspase activation. Together, these findings demonstrate that BAY 43-9006 mediates cell death in human leukemia cells, at least in part, through down-regulation of Mcl-1 via inhibition of translation. [ABSTRACT FROM AUTHOR]

Treatment with the protein kinase C activator 12-O-tetradecanoylphorbol 12-acetate (TPA) enables radiation-resistant LNCaP human prostate cancer cells to undergo radiation-induced apoptosis, mediated via activation of the enzyme ceramide synthase (CS) and de novo synthesis of the sphingolipid ceramide (Garzotto, M., Haimovitz­Friedman, A., Liao, W. C., White­Jones, M., Huryk, R, Heston, D. W. Wo, Cardon­Cardo, C., Kolesnick, R., and Fuks, Z. (1999) Cancer Res. 59, 5194–5201). Here, we show that TPA functions to decrease the cellular level of the ATM (ataxia telangiectasia mutated) protein, known to repress CS activation (Liao, W.-C., Haimovitz­ Friedman, A., Persaud, R., McLoughlin, M., Ehleiter, D., Zhang, N., Gatei, M., Lavin, M., Kolesnick, R., and Fuks, Z. (1999) J. Biol. Chem. 274, 17908–17917). Gel shift analysis in LNCaP and CWR22-Rv1 cells demonstrated a significant reduction in DNA binding of the Sp1 transcription factor to the ATM promoter, and quantitative reverse transcription-PCR showed a 50% reduction of ATM mRNA between 8 and 16 h of TPA treatment, indicating that TPA inhibits ATM transcription. Furthermore, treatment of LNCaP, CWR22-Rv1, PC-3, and DU-145 human prostate cells with antisense-ATM oligonucleotides, which markedly reduced cellular ATM levels, significantly enhanced radiation-induced CS activation and apoptosis, leading to apoptosis at doses as a low as 1 gray. These data suggest that the CS pathway initiates a generic mode of radiation-induced apoptosis in human prostate cancer cells, regulated by a suppressive function of ATM, and that ATM might represent a potential target for pharmacologic inactivation with potential clinical applications in human prostate cancer. [ABSTRACT FROM AUTHOR]

NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor β superfamily, is involved in cellular processes such as inflammation, apoptosis/survival, and tumorigenesis and is regulated by p53, Sp1, and Egr-1. In the current study, the regulation of NAG-1 expression in LNCaP human prostate carcinoma cells by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was examined. TPA treatment increased NAG-1 protein and mRNA levels in a time- and concentration-dependent manner as well as NF-κB binding/transcriptional activity in LNCaP cells. Pretreatment with protein kinase C (PKC) inhibitor blocked the TPA-induced increase in NAG-1 protein levels and NF-κB binding/transcriptional activity, whereas an inhibition of p38, JNK, MEK activity had no effect on TPA-induced NAG-1 levels and NF-κB transcriptional activity. Expression of constitutively active PKCs induced an increase in NF-κB transcriptional activity and NAG-1 protein levels in LNCaP cells. The expression of NF-κB p65 induced NAG-1 promoter activity, and chromatin immunoprecipitation assay for p65 showed that NF-κB binds the NAG-1 promoter in LNCaP cells. Inhibition of TPA-induced NAG-1 expression by NAG-1 short interfering RNA blocked TPA-induced apoptosis in LNCaP cells, suggesting induction of NAG-1 negatively affects LNCaP cell survival. These results demonstrate that NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-κB. [ABSTRACT FROM AUTHOR]

In this issue of Cancer Cell, Hatley et al., by using several tour-de-force in vivo approaches, reported a miR-21-mediated oncogenic pathway through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis in lung cancers models. Targeting miR-21 could be a promising therapeutic strategy in lung cancers. [Copyright &y& Elsevier]

The mortality rate caused by colorectal cancer is increasing. The current treatment options not only do not produce optimal results but also cause various side effects. Nowadays, herbal plants have been shown to be one of many treatment options, one of which is the Kersen plant ( Muntingia calabura L). This study aimed to evaluate the growth inhibitory effects and apoptosis induction ability of the methanolic extract on the WiDr colorectal cancer cell line, and also determine some of the secondary metabolites constituents. Antiproliferative activity was measured by 3-(4-dimethylthiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT) assay and apoptosis induction was detected by fluorescence microscopy (acridine orange/ethidium bromide, double staining method). Secondary metabolite content was evaluated by using spectrophotometry and thin layer chromatography (TLC). Alkaloids, flavonoids, saponin, and triterpenoids were identified in the methanolic extract. The methanolic extract was found to be cytotoxic to WiDr cells in a dose-dependent manner with IC 50 values from two experiments of 39.21 μg/mL and 40.22 μg/mL. The extract also caused typical apoptotic morphological changes in the WiDr colorectal cancer cell line. The results indicate that Muntingia calabura L may constitute a promising anticancer therapy in colorectal cancer. [ABSTRACT FROM AUTHOR]