Antiproliferative effect of Erycibe elliptilimba on human breast cancer cell lines

Erycibe elliptilimba Merr. & Chun., family Convolvulaceae, is a Thai traditional medicine which has long been prescribed for various infectious and malignant diseases. Bio-assays of extracts from Erycibe elliptilimba Merr. & Chun. showed that a fraction (fraction 3) from an methanolic extract had an antiproliferative effect on SKBR3 and MDA-MB435 human breast cancer cells. The ED50 value of Erycibe elliptilimba Merr. & Chun. fraction 3 was 56.07 and 30.61 μg/ml for SKBR3 and MDA-MB435, respectively. After 48 h of exposure, this fraction at a concentration of 100 μg/ml significantly reduced cell proliferation in both cancer cells. In MDA-MB435 cells, cell cycle analysis showed that the herb extract fraction 3 induced the accumulation of cells in G2/M phase, whereas no significant change in cell cycle was detected in SKBR3 cells. The results indicated that the extract fraction 3 could induce cell cycle arrest in some way. However, further investigation is needed to assess the molecular mechanisms mediated anticancer activities of this plant.     

Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit

A 70% methanol extract of Terminalia chebula fruit, was studied for its effects on growth in several malignant cell lines including a human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a non-tumorigenic, immortalized human prostate cell line (PNT1A) using assays for proliferation ([(3)H]-thymidine incorporation and coulter counting), cell viability (ATP determination) and cell death (flow cytometry and Hoechst DNA staining). In all cell lines studied, the extract decreased cell viability, inhibited cell proliferation, and induced cell death in a dose dependent manner. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. ATP assay guided chromatographic fractionation of the extract yielded ellagic acid, 2,4-chebulyl-beta-D-glucopyranose (a new natural product), and chebulinic acid which were tested by ATP assay on HOS-1 cell line in comparison to three known antigrowth phenolics of Terminalia, gallic acid, ethyl gallate, luteolin, and tannic acid. Chebulinic acid (IC(50) = 53.2 microM +/- 0.16) > tannic acid (IC(50) = 59.0 microg/ml +/- 0.19) > and ellagic acid (IC(50) = 78.5 microM +/- 0.24), were the most growth inhibitory phenolics of T. chebula fruit in our study.     

Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity

Twelve xanthone constituents of the botanical dietary supplement mangosteen (the pericarp of Garcinia mangostana) were screened using a noncellular, enzyme-based microsomal aromatase inhibition assay. Of these compounds, garcinone D (3), garcinone E (5), alpha-mangostin (8), and gamma-mangostin (9) exhibited dose-dependent inhibitory activity. In a follow-up cell-based assay using SK-BR-3 breast cancer cells that express high levels of aromatase, the most potent of these four xanthones was gamma-mangostin (9). Because xanthones may be consumed in substantial amounts from commercially available mangosteen products, the consequences of frequent intake of mangosteen botanical dietary supplements require further investigation to determine their possible role in breast cancer chemoprevention.     

Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria

Propionibacterium acnes and Staphylococcus epidermidis have been recognized as pus-forming bacteria triggering an inflammation in acne. The present study was conducted to evaluate antimicrobial activities of Thai medicinal plants against these etiologic agents of acne vulgaris. Crude extracts were tested for antimicrobial activities by disc diffusion and broth dilution methods. The results from the disc diffusion method showed that 13 medicinal plants could inhibit the growth of Propionibacterium acnes. Among those, Senna alata, Eupatorium odoratum, Garcinia mangostana, and Barleria lupulina had strong inhibitory effects. Based on a broth dilution method, the Garcinia mangostana extract had the greatest antimicrobial effect. The MIC values were the same (0.039 mg/ml) for both bacterial species and the MBC values were 0.039 and 0.156 mg/ml against Propionibacterium acnes and Staphylococcus epidermidis, respectively. In bioautography assay, the Garcinia mangostana extract produced strong inhibition zones against Propionibacterium acnes. Antimicrobial activity from fractions of column chromatography revealed one of the active compounds in Garcinia mangostana could be mangostin, a xanthone derivative. Taken together, our data indicated that Garcinia mangostana had a strong inhibitory effect on Propionibacterium acnes and Staphylococcus epidermidis. Therefore, this plant would be an interesting topic for further study and possibly for an alternative treatment for acne.     

Plumbagin induces apoptosis in Her2-overexpressing breast cancer cells through the mitochondrial-mediated pathway

Breast cancer is the leading cause of death-related cancers in women. Approximately 30% of breast cancers overexpress the Her2 oncogene, which is associated with a poor prognosis and increased resistance to chemotherapy. Plumbagin (1), a constituent of species in the plant genera Drosera and Plumbago, displays antineoplastic activity toward various cancers. The present study was aimed at determining the anticancer potential of 1 toward Her2-overexpressing breast cancer cells and defining the mode of cell death induced in these cells. The results showed that 1 exhibited high antiproliferative activity toward the Her2-overexpressing cell lines SKBR3 and BT474. The antiproliferative activity of 1 was associated with apoptosis-mediated cell death, as revealed by caspase activation and an increase in the sub-G1 fraction of the cell cycle. Compound 1 increased the levels of the proapoptotic Bcl-2 family of proteins and decreased the level of the antiapoptotic Bcl-2 protein in SKBR3 and BT474 cells. Thus, these findings indicate that 1 induces apoptosis in Her2-overexpressing breast cancers through the mitochondrial-mediated pathway and suggest its potential for further investigation for the treatment of Her2-overexpressing breast cancer.     

Typhonium flagelliforme inhibits cancer cell growth in vitro and induces apoptosis: an evaluation by the bioactivity guided approach

AIM OF THE STUDY: Typhonium flagelliforme (Lodd.) Blume (Araceae) is a Malaysian plant used locally to combat cancer. In order to evaluate its antiproliferative activity in vitro and to possibly identify the active chemical constituents, a bioactivity guided study was conducted on the extracts of this plant. MATERIALS AND METHODS: The active extracts of Typhonium flagelliforme were fractionated by flash column chromatography and each fraction was evaluated for antiproliferative activity using MTT assay. The apoptotic effect of the active fraction was determined microscopically and by using TUNEL colorimetric assay. GC-MS and NMR were used to determine the chemical constituents of this active fraction. RESULTS: Several fractions of the hexane and dichloromethane extracts were found to inhibit the growth of NCI-H23 non-small cell lung carcinoma cell line significantly, with IC(50)<15 microg/ml. However, most of these active fractions were also found to inhibit the growth of non-tumorigenic BALB/c 3T3 mouse fibroblast cell line except for fraction 21 of the dichloromethane extract (D/F21). This particular fraction was not only less cytotoxic to the non-tumorigenic cells, where the IC(50) was 48.6 microg/ml compared to IC(50) 7.5 microg/ml for NCI-H23, but it was also found to induce apoptosis in the cancer cell line. GC-MS analysis revealed that D/F21 contains hexadecanoic acid, 1-hexadecene, phytol and a derivative of phytol. The presence of non-saturated fatty acids in this fraction was confirmed by nuclear magnetic resonance spectroscopy. CONCLUSIONS: D/F21 was found to be the active and cancer cell line specific fraction of Typhonium flagelliforme. Its major chemical constituents had been determined spectroscopically.     

The extract of Hibiscus syriacus inducing apoptosis by activating p53 and AIF in human lung cancer cells

Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC(50) values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 microg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 microg/ml) induced A549 cell apoptosis to 48 +/- 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.     

Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines

We examined the effects of six xanthones from the pericarps of mangosteen, Garcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60. All xanthones displayed growth inhibitory effects. Among them, alpha-mangostin showed complete inhibition at 10 microM through the induction of apoptosis.     

Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line

Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.     

In vitro cytotoxic, antileishmanial and antifungal activities of ethnopharmacologically selected Gabonese plants

Seventy-seven crude extracts from leaves and stem barks of 15 Gabonese plants used in traditional medicine were evaluated for their cytotoxic, antileishmanial and antifungal activities. Most of the extracts exhibited cytotoxic activities toward human monocytes, and most particularly the hydromethanolic 50% (v/v) fraction of Ganophyllum giganteum leaves (IC(50)=1.3 microg/ml) as well as the methanolic extracts of Polyalthia suaveolens, Dioscorea preussii, Augouardia letestui leaves and Cola lizae stem barks (IC(50)<5 microg/ml). The methanolic extract of Polyalthia suaveolens displayed a strong antiproliferative activity against the promastigote form of Leishmania infantum parasites and presented a good antifungal activity on all the tested strains (IC(50)<1mg/ml). This extract was divided into six fractions: fraction F6 demonstrated a cytotoxic activity stronger than those of the crude extract (IC(50)=0.6 microg/ml), fractions F4 and F5 were devoid of cytotoxicity (IC(50)>100 microg/ml) and displayed interesting antileishmanial activity against the intracellular amastigote form of the parasite (IC(50)=5.6 and 12.4 microg/ml), respectively. However, the antifungal activity observed for the crude extract could not be recovered in the corresponding fractions.