1. Protease inhibitors and carcinoma of the esophagus.
Squamous cell carcinoma of the esophagus is endemic in parts of South Africa. Previous case-control studies have shown many associations but no clear etiologic pathway has been established. A case-control study of dietary and social factors was performed for 130 patient/control pairs matched for age, gender, and educational level. Staple diet, consumption of wild vegetables, use of tobacco, and traditional beer consumption were compared between the two groups. The results showed that new significant associations were found with the consumption of beans (P = 0.016) and consumption of the full traditional diet of maize, pumpkin, and beans (P = 0.027). Known associations with the consumption of Solanum nigrum (P = 0.018) and with smoking (P = 0.002) were confirmed by multiple regression analysis. It’s concluded that Solanum nigrum, beans, and pumpkin all contain protease inhibitors. Suppression of protease inhibitors can lead to overexpression of growth factors in the esophagus, resulting in a proliferative and oncogenic drive.
––Sammon AM. Cancer 1998 Aug 1;83(3):405-8
2. Sultana S, Perwaiz S, Iqbal M, Athar M. Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus inhibit free radical-mediated DNA damage. J Ethnopharmacol 1995 Mar;45(3):189-92.
The presence of plant extracts of Solanum nigrum and Cichorium intybus in the reaction mixture containing calf thymus DNA and free radical generating system protect DNA against oxidative damage to its deoxyribose sugar moiety. The effect was dependent on the concentration of plant extracts. However, the effect of Cichorium intybus was much pronounced as compared to the effect of Solanum nigrum. These studies suggest that the observed hepatoprotective effect of these
crude plant extracts may be due to their ability to suppress the oxidative degradation of DNA in the tissue debris.
1. Lu CM, Yang JJ, Wang PY, Lin CC. A new acylated flavonol glycoside and antioxidant effects of Hedyotis diffusa. Planta Med 2000 May;66(4):374-7.
A study on the bioactive principles of Hedyotis diffusa Willd., led to the isolation of a new acyl flavonol di-glycoside which was characterized as kaempferol 3-O[2"-O-(E-6'"-O-feruloyl)-beta-D-glucopyranosyl]-beta-D-galactop yranoside by spectral and chemical methods from the methanolic extract. In addition, three known flavonol glycosides and six known iridoid glycosides were also obtained. The above-mentioned glycosides were tested for antioxidant effects on xanthine oxidase inhibition, xanthine-xanthine oxidase cytochrome c and TBA-MDA systems.
2. Han F, Hu J, Xu H. Effects of some Chinese herbal medicine and green tea antagonizing mutagenesis caused by cigarette tar. Zhonghua Yu Fang Yi Xue Za Zhi. 1997 Mar;31(2):71-4.
Anti-mutagenic effects of some Chinese herbal medicine and green tea antagonizing cigarette tar was studied with unscheduled DNA synthesis (UDS) test in human peripheral lymphocytes in order to exploit the better use of Chinese herbal resources. Results showed that Scutellaria barbata, Hedyotis diffusa wildi, Xihuangwan, green tea and tea polyphenol all had anti-mutagenic effects,
to some extent. And, 125 g/L of Scutellaria barbata, 125 g/L Hedyotis diffusa wildi, 325 g/L Xihuangwan, 78 g/L green tea and 25 g/L tea polyphenol could inhibit obviously the damage to DNA in lymphocytes caused by the total particle material (TPM) extracted from cigarette tar. If the Chinese herbal medicine and green tea were injected into cigarettes beforehand, extracted TPM (containing herbal medicine and green tea) also could protect DNA in lymphocytes from damage caused by cigarette tar, to even greater extent. This result is basically consistent with other anti-mutagenesis tests.
1. Anticancer activity of Scutellaria baicalensis and its potential mechanism.
OBJECTIVE: Scutellaria baicalensis is a widely used Chinese herbal medicine that historically is used in anti-inflammatory and anticancer therapy. The aim of the study is to determine its ability to inhibit human cancer cells in vitro and to determine whether its anticancer activity is because of the inhibition of prostaglandin E(2) (PGE(2)) production that is derived from arachidonic acid through cyclooxygenase-2 (COX-2) pathway. METHODS: Cell lines from the most common human cancers, including squamous cell carcinoma (SCC-25, KB), breast cancer (MCF-7), hepatocellular carcinoma (HepG2), prostate carcinoma (PC-3 and LNCaP), and colon cancer (KM-12 and HCT-15) were tested. The cells were treated with various concentrations of Scutellaria baicalensis (0.1-100 mg/mL) for 72 hours. Percentage of viable cells after treatment was assessed using a trypan blue dye exclusion assay and the level of PGE(2) production was determined by enzyme immunoassay (EIA). RESULTS: Scutellaria baicalensis demonstrated a strong dose-dependent growth inhibition in all cell lines. Inhibition concentration at 50% (IC(50)) for HepG2, MCF-7, PC-3, LNCaP, KM-12, HCT-15, KB and SCC-25 cells was 1.1, 0.9, 0.52, 0.82, 1.1, 1.5, 1.0, and 1.2 mg/mL, respectively. Three cell lines (KB, SCC-25, and HepG2) were assessed for the production of PGE(2) and a high level of extracellular (KB and SCC-25) and intracellular PGE(2) (HepG2) was noted. In the presence of Scutellaria baicalensis extract, there was a significant decrease of PGE(2) in a dose-dependent fashion. CONCLUSIONS: Scutellaria baicalensis strongly inhibits cell growth in all cancer cell lines tested. However, prostate and breast cancer cells (PC-3, LNCaP, and MCF-7) are slightly more sensitive than other type of cancer cells. It also inhibits PGE(2) production, indicating that suppression of tumor cell growth may be due to its ability to inhibit COX-2 activity. This study supports the notion of using Scutellaria baicalensis as a novel anticancer agent to treat various cancers.
––Ye F, Xui L, Yi J, Zhang W, Zhang DY. J Altern Complement Med. 2002 Oct;8(5):567-72.
2. Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin.
The flavonoid baicalin (baicalein 7-D-beta-glucuronate) is isolated from the dried root of Scutellaria baicalensis Georgi (Huang Qin). In the present study, we investigated the in vitro effects of baicalin on the growth, viability, and induction of apoptosis in several human prostate cancer cell lines, including DU145, PC-3, LNCaP and CA-HPV-10. The cell viability after treating with baicalin for 2-4 days was quantified by a colorimetric 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium (MTS) assay. The results showed that baicalin could inhibit the proliferation of prostate cancer cells. The responses to baicalin were different among different cell lines, with DU145 cells being the most sensitive and LNCaP cells the most resistant. Baicalin caused a 50% inhibition of DU145 cells at concentrations of 150 microM or above. The inhibition of proliferation of prostate cancer cells after a short period of exposure to baicalin was associated with induction by apoptosis, as evidenced by the typical nuclear fragmentation using Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling, DNA fragmentation, activation of caspase-3 and cleavage of poly-ADP-ribose polymerase (PARP). The results indicate that baicalin has direct anti-tumor effects on human prostate cancer cells.
––Chan FL, Choi HL, Chen ZY, Chan PS, Huang Y. Cancer Lett. 2000 Nov 28;160(2):219-28.
1. Isolation of two cytotoxic diterpenes from the fern Pteris multifida.
From aerial parts of the fern Pteris multifida Poir. (Polypodiaceae) two diterpenes, entkaurane-2 beta, 16 alpha-diol and ent-kaur-16-ene-2 beta, 15 alpha-diol, were isolated by repeated column chromatography using silica gel and silica gel impregnated with silver nitrate. The structures were confirmed by spectroscopic methods. Both compounds showed a moderate cytotoxicity to Ehrlich ascites tumour cells.
––Woerdenbag HJ, Lutke LR, Bos R, Stevens JF, Hulst R, Kruizinga WH, Zhu YP, Elema ET, Hendriks H, van Uden W, Pras N. Z Naturforsch [C]. 1996 Sep-Oct;51(9-10):635-8.
1. Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma.
We examined the effect of berberine, a major component with anti-fungal properties contained in Coptidis Rhizoma and Phellodendri Cortex, on the lymph node metastasis of murine lung cancer. Oral administration of berberine for 14 days significantly inhibited the spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma (LLC) into the lung parenchyma in a dose-dependent manner, but did not affect the tumor growth at the implantation site of the lung. Combined treatment with berberine and an anti-cancer drug, CPT-11, resulted in a marked inhibition of tumor growth at the implantation site and of lymphatic metastasis, as compared with either treatment alone. Anti-activator protein-1 (anti-AP-1) transcriptional activity of non-cytotoxic concentrations of berberine caused the inhibition of the invasiveness of LLC cells through the repression of expression of urokinase-type plasminogen activator (u-PA).
––Mitani N, Murakami K, Yamaura T, Ikeda T, Saiki I. Cancer Lett. 2001 Apr 10;165(1):35-42.
2. Screening new photosensitizers from Chinese medicinal herbs and searching for herbal photodynamic killing effects on human stomach cancer cells
OBJECTIVE: To find new photosensitizers from Chinese medicinal herbs for cancer photodynamic therapy. METHODS: The extracts of thirteen herbs were examined: (1) Their fluorescence excitation wave lengths and emission wave lengths; (2) Their fluorescence intensity in living cells and (3) Their distribution and localization in the living cells and the fixed cells both stained in each extract, and responses of cell fluorescence intensity to pH value change. Furthermore, the herb's anticancer photosensitive efficiencies were studied by using BCG-823 human stomach cancer cells. RESULTS: Cortex phellodendri and Rhizoma Coptidis, were found with optimal fluorescence properties as photosensitizers in this test. The latter could remarkably reduce the cell metabolic viability, proliferative ability and increased the cell mortality when the cells exposed to both drugs and luminance but not only to drug. CONCLUSIONS: The potential of Chinese medicine as new kind of photosensitizer and its possibility for use in anticancer photodynamic therapy are existed.
––Liao J, Li PP, Wu CJ. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Dec;17(12):726-9.
1. Inhibition of tumor growth by S-3-1, a synthetic intermediate of salvianolic acid A.
Salvianolic acid A (1) is one of the active components from Salvia miltiorrhiza, which was found to suppress the growth of mouse tumors. S-3-1 (a 2-allyl-3,4-dihydroxybenzaldehyde, 2) is a synthetic intermediate of a salvianolic acid A derivative with strong inhibitory effects on the growth of cancer cells in vitro. The inhibitory effects of 2 on tumor growth and its molecular targets were studied. 2 significantly suppressed the growth of mouse Lewis lung carcinoma, S180 sarcoma and H22 hepatic carcinoma in a dose-dependent manner. With a simple scrape-loading dye transfer method, 20 microg/ml of 2 was found to significantly enhance gap junction intercellular communication (GJIC) in human pancreatic adenocarcinoma PaCa Cells, human lung epithelial carcinoma W1-38 cells and human lung adenocarcinoma A549 cells, but 2 had no marked effect on GJIC in human colon cancer CACO2 cells. With Northern blot analysis, 2 was found to inhibit the expression of c-myc gene in A549 cells and have no marked effect on H-ras oncogene expression, and increase the cellular P53 mRNA contents, though it did not affect the expression of RB tumor suppressor gene. 2 also suppressed the P46 (JNK/SAPK) expression in A549 cells. Western blot analysis was applied to visualize the P21ras protein. Results shows that 2 at concentrations ranging from 10 to 20 microg/ml decreases the contents of the membranous P21ras and total P21ras and increases the contents of cytosolic P21ras protein in a time-dependent manner. However, 2 had no significant effects on farnesyl protein transferase activities at the concentrations that could efficiently decrease the membranous P21ras content. This suggested that 2 might suppress tumor growth partly through enhancement of GJIC and reversion of the transformed phenotypes. The other mechanisms may be that 2 can suppress the overexpression of c-myconcogene, inhibit the function of Ras oncoprotein, increase the expression of P53 tumor suppressor gene and interrupt P46-associated mitogen-activated pathway other than farnesylation of Ras protein.
––Li HY, Li Y, Yan CH, Li LN, Chen XG. J Asian Nat Prod Res. 2002 Dec;4(4):271-80.
2. Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells.
Salvia miltiorrhiza (SM) is a traditional Chinese herbal medicine, commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that SM exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of SM in a human hepatoma cell line, HepG(2). Our results show that SM exerted clear cytotoxic effects, and strongly inhibited the proliferation of HepG(2) cells. It was also observed that SM treatment caused apoptotic cell death as evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G(1) cell analysis. Furthermore, depletion of intracellular glutathione (GSH) and reduction of mitochondrial membrane potential were found to be involved in the initiation of apoptosis by SM.
––Liu J, Shen HM, Ong CN. Cancer Lett. 2000 May 29;153(1-2):85-93.