Phytochemicals investigation on rhizomes of Alpinia mutica has afforded five compounds namely 5,6-dehydrokawain (1), flavokawin B (2), pinostrobin (3) and pinocembrin (4) together with β-sitosterol (5). All crude extracts of the plant demonstrated strong cytotoxicity against CEMss (human T4 lymphoblastoid) cancer cells with IC50 values less than 19 μg/mL, while flavokawin B (2) was the most cytotoxic isolate with IC50 value 1.86±0.37 μg/mL. Most of the crude extracts and isolated compounds showed weak activity in antimicrobial and diphenylpicrylhydrazyl (DPPH) radical scavenging activity tests.
Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain (C6), using 5-fluorouracil as positive control. Pronounced antiproliferative activities were observed for compound 1 which exhibited a comparable activity with the positive control, against brain (C6) and colorectal (SW48, KM12, HCT116) cancer cell lines showing IC50 values in the range of 14 to 65μM. Meanwhile, compound 5 displayed a greater cytotoxic effect showing at least 2-fold more strongly than the positive control, against C6 brain cancer cells. The assay findings have unveiled the therapeutic value of phytochemicals from Calophyllum castaneum as anti-cancer agents.
Cyathula prostrata (Linn) Blume herbs are commonly used for the treatment of inflammatory and pain in Nigeria. The objective of the present study was to assess the antitumor and antioxidant activity of Cyathula prostrata (Linn) Blume in mice model. The treatment of Dalton's lymphoma ascites cells induced tumor by the methanolic extract of Cyathula prostrata was determined at concentration of 100 mg/ kg body weight given orally for 11 days, antitumor activity was assessed by monitoring the mean survival time, body weight, effect on hematological parameters, antioxidant enzyme levels and histopathological evidence. The results showed that the methanolic extract of Cyathula prostrata increased the survival period of animals, decreased the body weight and also altered many hematological markers and also restored the antioxidant enzymes when compared to the mice of the DLA control group. These findings indicate that the methanolic extract of C. prostrata has anti-tumor activity by preventing the lipid peroxidation and thereby promoting the antioxidant systems in Dalton's lymphoma ascites induced mice. So, these extract could be a natural anticancer agent for human health.
Structure-activity relationships of eleven xanthones were comparatively predicted for four cancer cell lines after the compounds were subjected to antiproliferative assay against B-lymphocyte cells (Raji), colon carcinoma cells (LS174T), human neuroblastoma cells (IMR-32) and skin carcinoma cells (SK-MEL-28). The eleven chemical constituents were obtained naturally from the stem bark of Calophyllum inophyllum and Calophyllum soulattri. Inophinnin (1) and inophinone (2) were isolated from Calophyllum inophyllum while soulattrin (3) and phylattrin (4) were found from Calophyllum soulattri. The other xanthones were from both Calophyllum sp. and they are pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7), 4-hydroxyxanthone (8), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). Compound 3 was found to be the most cytotoxic towards all the cancer cell lines with an IC50 value of 1.25μg/mL while the simplest xanthone, compound 8 was inactive.
Seaweeds have been used by mankind as medicine and food for more than 13,000 years. Marine algae are considered to produce a valuable phytoconstituents characterized by a broad spectrum of antitumor activities. The aim of the present study was to explore the effect of different solvent extracts of Sargassum wightii, Greville against Dalton's Ascitic Lymphoma (DAL) in Swiss male albino mice. DAL cells were injected intraperitoneally 1 x10(6) cell to the mice. Two days after cells injection the animals were treated with different solvent extracts of Sargassum wightii at dose of 200 mg kg(-1) for 14 days. 5-fluorouracil (20 mg kg(-1)) was used as reference drug. On day 11, cancer cell number, packed cell volume, decrease in tumour weight of the mice, increase in life span and hematological parameters were evaluated and compared with the same parameters in control. A significant increase in the life span and a decrease in the cancer cell number and tumour weight were noted in the tumour-induced mice after treatment with the extract. The haematological parameters were also normalized by the ethanolic and chloroform extracts in tumour-induced mice. These observations are suggestive of the protective effect of ethanolic extract of Sargassum wightii is comparatively better than other two tested extracts against Dalton's Ascitic Lymphoma (DAL).
A cytotoxic bisindole alkaloid possessing an unprecedented structure constituted from the union of an eburnan half and a novel vinylquinoline alkaloid has been isolated from Leuconotis griffithii. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway to the novel quinolinic coupling partner is presented from an Aspidosperma precursor.
Deregulated cell signaling pathways result in cancer development. More than one signal transduction pathway is involved in colorectal cancer pathogenesis and progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene triterpene isolated from the Sandoricum koetjape stem bark. We report the cellular and molecular mechanisms of anticancer activity of KA towards human colorectal cancer. The results showed that KA induces apoptosis in HCT 116 colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic caspases. We confirmed that KA-induced apoptosis was mediated by DNA fragmentation, nuclear condensation and disruption in the mitochondrial membrane potential. Further studies on the effect of KA on cancer pathways show that the compound causes down-regulation of Wnt, HIF-1α, MAP/ERK/JNK and Myc/Max signaling pathways and up-regulates the NF-κB signaling pathway. The result of this study highlights the anticancer potential of KA against colorectal cancer.
The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 10(6) cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.
Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
The incidence of prostate cancer malignancy along with other cancer types is increasing worldwide, resulting in high mortality rate due to lack of effective medications. Moringa oleifera has been used for the treatment of communicable and non-communicable ailments across tropical countries, yet, little has been documented regarding its effect on prostate cancer. We evaluated the acute toxicity and apoptosis inducing effect of glucomoringin-isothiocyanate rich soluble extracts (GMG-ITC-RSE) from M. oleifera in vivo and in vitro, respectively. Glucomoringin was isolated, identified, and characterized using fundamental analytical chemistry tools where Sprague-Dawley (SD) rats, murine fibroblast (3T3), and human prostate adenocarcinoma cells (PC-3) were used for acute toxicity and bioassays experiments. GMG-ITC-RSE did not instigate adverse toxic reactions to the animals even at high doses (2000 mg/kg body weight) and affected none of the vital organs in the rats. The extract exhibited high levels of safety in 3T3 cells, where more than 90% of the cells appeared viable when treated with the extract in a time-dependent manner even at high dose (250 µg/mL). GMG-ITC-RSE significantly triggered morphological aberrations distinctive to apoptosis observed under microscope. These findings obviously revealed the putative safety of GMG-ITC-RSE in vivo and in vitro, in addition to its anti-proliferative effect on PC-3 cells.
Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several invitro and invivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.
A new chromanone acid, namely caloteysmannic acid (1), along with three known compounds, calolongic acid (2), isocalolongic acid (3) and stigmasterol (4) were isolated from the stem bark of Calophyllum teysmannii. All these compounds were evaluated for their cytotoxic and antioxidant activities in the MTT and DPPH assays, respectively. The structure of compound 1 was determined by means of spectroscopic methods including 1D and 2D NMR experiments as well as HR-EIMS spectrometry. The stereochemical assignment of compound 1 was done based on the NMR results and X-ray crystallographic analysis. The preliminary assay results revealed that all the test compounds displayed potent inhibitory activity against HeLa cancer cell line, in particular with compound 1 which exhibited the highest cytotoxic activity comparable to the positive control used, cisplatin. However, no significant antioxidant activity was observed for all the test compounds in the DPPH radical scavenging capacity assay.
Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
Extensive chromatographic isolation and purification of the extracts of the stem bark of Calophyllum inophyllum and Calophyllum soulattri have resulted in 11 xanthones. C. inophyllum gave inophinnin (1), inophinone (2), pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7) and 4-hydroxyxanthone (8), while C. soulattri afforded soulattrin (3), phylattrin (4), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D NMR, GC-MS, IR and UV. Cytotoxicity screening (MTT assay) carried out in vitro on all the xanthones using five human cancer cell lines indicated good activities for some of these xanthones. The structure-activity relationship study revealed that the inhibitory activities exhibited by these xanthone derivatives to be closely related to the existence and nature of the pyrano and the prenyl substituent groups on their skeleton.
A new triterpene, malaytaraxerate (1), and four known compounds, taraxerol (2), taraxerone (3), docosyl isoferulate (4) and docosanoic acid 2',3'-dihydroxypropyl ester (5), were isolated from the acetone extract of Sapium baccatum stem bark. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-Vis, FT-IR, 1D and 2D NMR, and mass spectrometry. Major isolated compounds were assayed for cytotoxicity. The chemotaxonomic significance of this plant was also studied.
A new sesquiterpenoid, malayscaphiol (1), and three known compounds, lupeol (2), lupenone (3) and stigmasterol (4), were isolated from the methanolic extract of the stem bark of Scaphium macropodum. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-vis, FT-IR, 1D and 2D NMR, and mass spectrometer. Major isolated compounds were assayed for cytotoxicity and anti-acetylcholinesterase activities. The chemotaxonomy significance of this plant was also discussed.
A new furanodihydrobenzoxanthone, artomandin (1), together with three other flavonoid derivatives, artoindonesianin C, artonol B, and artochamin A, as well as β-sitosterol were isolated from the stem bark of Artocarpus kemando. The structures of these compounds were determined on the basis of spectral evidence. All of these compounds displayed inhibition effects to a very susceptible degree in cancer cell line tests. Compound 1 also exhibited significant antioxidant capacity in the free radical 1,1-diphenyl-2-picrylhydrazyl tests.
Curcuma ochrorhiza ('temu putih') and C. heyneana ('temu giring') are two Zingiberaceous species which are commonly used in traditional medicine in Malaysia and Indonesia. Phytochemical investigations on these Curcuma species have resulted in the isolation of six sesquiterpenes, namely zerumbone (1), furanodienone (2), zederone (3), oxycurcumenol epoxide (4), curcumenol (5) and isocurcumenol (6), along with phytosterols stigmasterol and alpha-sitosterol. Compounds 1 and 2 were obtained for the first time for C. ochrorhiza while 4 was new to C. heyneana. The hexane extract of C. ochrorhiza and sesquiterpenes 1 and 3 showed very strong cytotoxicity activity against T-acute lymphoblastic leukaemia cells (CEM-SS), with IC(50) values of 6.0, 0.6 and 1.6 microg mL(-1), respectively. Meanwhile, constituents from C. heyneana (4-6) demonstrated moderate inhibition against CEM-SS in cytotoxic assay, with IC(50) values of 11.9, 12.6 and 13.3 microg mL(-1), respectively. The crude extracts and sesquiterpenes isolated were moderately active against certain bacteria tested in antimicrobial screening.
Investigation on the leaves of Melicope bonwickii (F.Muell.) T.Hartley (Rutaceae) afforded a new 7-(2'-hydroxy-3'-chloroprenyloxy)-4-methoxyfuroquinoline (1) together with the known 7-(2',3'-epoxyprenyloxy)-4-methoxyfuroquinoline (2), evellerine (3) kokusaginine (4) and an amide aurantiamide acetate (5). Compounds 1 and 2 showed significant activity against cervical cell lines (Hela).
Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC50 of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC50 = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).