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. 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. The cytotoxicity of methyl protoneodioscin (NSC-698791) against human cancer cell lines in vitro.
Methyl protoneodioscin (NSC-698791) is a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of the urinary bladder and renal tumor for centuries. In order to systematically evaluate its potential anticancer activity, methyl protoneodioscin cytotoxicity was tested in vitro against 60 human cancer cell lines in the NCI's (National Cancer Institute, USA) anticancer drug screen. As a result, methyl protoneodioscin was cytotoxic against all the test cell lines from leukemia and solid tumors in the NCI's human cancer panel, especially selectively against one non-small cell lung cancer (NSCLC) line (A549/ATCC), one colon cancer line (HCT-116), two central nenous system (CNS) cancer lines (SF-539 and SNB-75), one melanoma line (M14), one renal cancer line (CAKI-1), one prostate cancer (DU-145) and two breast cancer lines (HS 578T and MDA-MB-435) with GI50 < or = 2.0 microM. The selectivity between these nine most sensitive lines and the least sensitive line (TK-10) was from 22- to 30- fold. In the same cancer subpanel, a selectivity at GI50 level of more than 15-fold was observed between A549/ATCC and EKVX (NSCLC), between CAKI-1 and TK-10, A498 (renal cancer), respectively. In general the CNS cancer was the most sensitive subpanel, while renal cancer was the least sensitive subpanel.
––Hu K, Yao XS. Anticancer Res. 2002 Mar-Apr;22(2A):1001-5.
2. Antineoplastic agents; I. Three spirostanol glycosides from rhizomes of Dioscorea collettii var. hypoglauca.
By activity-guided fractionation, three known steroidal saponins, prosapogenin A of dioscin, dioscin and gracillin, were isolated from the total saponin fraction of Dioscorea coiletti var. hypoglauca as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic activity against the cancer cell line K562 in vitro. The structures of the compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H-NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis.
––Hu K, Dong A, Yao X, Kobayashi H, Iwasaki S. Planta Med. 1996 Dec;62(6):573-5.
3. Enhancement of oxidative response and cytokine production by yam mucopolysaccharide in murine peritoneal macrophage.
Yam (Dioscorea batatas) mucopolysaccharide (YMP) was examined for the ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various doses (10-100 microg/ml) of YMP for 48 h, a significant cytotoxicity against B 16 cells was observed. YMP also increased the myeloperoxidase activity and the production of H(2)O(2), O(2)(-), nitric oxide (NO) and tumor necrosis factor (TNF-alpha). However, there was a little alteration on the production of IFN-gamma. These results indicate that reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI) and TNF-alpha are likely major mediators of cytotoxic activity of YMP-treated macrophages.
––Choi EM, Hwang JK. Fitoterapia. 2002 Dec;73(7-8):629-37.
1. Effects of Rehmannia glutinosa polysaccharide b on T-lymphocytes in mice bearing sarcoma 180.
AIM: To study immuno-antitumor action mechanism of RGP-b. RGP-b (Rehmannia glutinosa polysaccaride b) is a new component isolated from the herb, had an average molecular mass of 160 kDa and 5 kinds of monosaccharides as acid-splitting products. Its HPLC showed a main sharp peak at 162 kDa. METHODS: The kinetic effects of RGP-b on IL-2 secretion, cytotoxic T-lymphocyte (CTL) activities and L3T4+, lyt-2+ T-lymphocyte subset in mice bearing S180 were observed. RESULTS: RGP-b 10 or 20 mg kg-1 ip obviously attenuated the decrease of CTL cytotoxity caused by excessive tumor growth on d 9 after the administration, but only partly ameliorated the descent of IL-2. Its effect on lyt-2+ subset was quite parallel with that on CTL cytotoxity. RGP-b kept the ratio of L3T4+ to lyt-2+ subset lower than that of control. CONCLUSION: Improving the production of lyt-2+ CTL and its cytotoxity were an essential immuno-antitumor mechanisms of RGP-b.
––Chen LZ, Feng XW, Zhou JH. Zhongguo Yao Li Xue Bao. 1995 Jul;16(4):337-40.
2. Effects of low-molecular-weight Rehmannia glutinosa polysaccharides on p53 gene expression
AIM: To study the effect of low-molecular-weight Rehmannia glutinosa polysaccharides (LRPS) on p53 gene expression. METHODS: The level of p53 gene expression was determined by quantitative polymerase chain reaction and autoradiography. RESULTS: The levels of p53 mRNA in Lewis lung cancer tissue were 0.46, 1.52, 1.48, and 1.60 respectively after saline, LRPS 20 and 40 mg.kg-1, and cyclophosphamide 10 mg.kg-1, which were the effective doses inhibiting the growth of tumor tissue cells in vivo. LRPS markedly increased p53 gene expression. CONCLUSION: LRPS effect on p53 gene expression is one of the mechanisms of antitumor activity.
––Wei XL, Ru XB. Zhongguo Yao Li Xue Bao. 1997 Sep;18(5):471-4.
3. 32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs
32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs were compared with 26 similar cases as control group. The drugs used in chemotherapy consisted of two regimens, DDP and high-dose MTX plus VCR. The results showed that the side effects of chemotherapy in control group were consistent with literatures; while the group treated with Chinese medicinal herbs suffered less toxic effects, the difference between two groups was statistically significant. The medicinal herbs used to reduce the side effects induced by DDP was Pinellia ternata, Amomum cardamomum, Bambusa textilis, Citrus reticulata etc.; while the herbs used to alleviate the adverse effects of high-dose MTX plus VCR was Gypsum, Anemarrhena asphodeloides, Rehmannia glutinosa, Ophiopogon japonicus, Scrophularia ningpoensis, etc.
––Liu JQ, Wu DW. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 Mar;13(3):150-2, 132.
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-promoting effects by poricoic acids G and H and other lanostane-type triterpenes and cytotoxic activity of poricoic acids A and G from Poria cocos.
The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3, 21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24–methyllanosta - 4(28),8,24 (24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.
––Ukiya M, Akihisa T, Tokuda H, Hirano M, Oshikubo M, Nobukuni Y, Kimura Y, Tai T, Kondo S, Nishino H. J Nat Prod. 2002 Apr;65(4):462-5.
2. Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.
Pachymic acid, 3-O-acetyl-16 alpha-hydroxytrametenolic acid, and poricoic acid B had been isolated from the sclerotium of Poria cocos Wolf. These compounds showed a strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. At 0.2 mumol/mouse, these compounds markedly inhibited the promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse).
––Kaminaga T, Yasukawa K, Kanno H, Tai T, Nunoura Y, Takido M. Oncology. 1996 Sep-Oct;53(5):382-5.
No related research.
1. Stimulating activity of Chinese medicinal herbs on human lymphocytes in vitro.
The effects of eight kinds of Chinese medicinal herbs (CMH) on human lymphocytes was studied in vitro. The extract of Cinnamomum cassia presl markedly stimulated human lymphocytes to proliferate. Codonopsis pilosula, Oldenlandia diffusa and Rhizoma typhonii weakly stimulated. These extracts enhanced cytotoxic T-lymphocyte (CTL) activity, but failed to enhance natural killer (NK)-cell activity. The extracts of these CMHs have stimulatory effect on immunoglobulin (Ig) production by B-cells and interleukin(IL)-1 production by monocytes. These activities of Cinnamomun cassia presl extract are associated with glycoproteins, whose molecular weight was about 100 KDa. These results suggest that CMH extracts have a stimulating activity on human lymphocytes and these abilities could be used clinically for the treatment of diseases such as cancer.
––Shan BE, Yoshida Y, Sugiura T, Yamashita U. Int J Immunopharmacol. 1999 Mar;21(3):149-59.
2. Immunological and hematopoietic effect of Codonopsis pilosula on cancer patients during radiotherapy]
Codonopsis pilosula was used as an adjuvant in 76 cancer patients during radiotherapy and its protective effect on hematopoietic and immunologic function was studied. Results: (1) No influence on Hb and WBC of the patients with radiotherapy. (2) It could reduce the immunosuppressive effect of radiotherapy on delayed hypersensitive reaction, the lymphocyte response to PHA and IL-2. (3) No difference between treated and control groups in most humoral immune indices such as IgG, IgA and C3, but had slight increase in IgM in treated patients, while significant decrease in control.
––Zneg XL, Li XA, Zhang BY. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992 Oct;12(10):607-8, 581.
1. In vitro and in vivo antitumoral phenanthrenes from the aerial parts of Dendrobium nobile.
Two phenanthrenes were isolated from the aerial part of Dendrobium nobile Lindl. and their structures were identified to be 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (1) and denbinobin (2), among which the former has been first isolated from this plant. These two compounds were found to be cytotoxic against A549 (human lung carcinoma), SK-OV-3 (human ovary adenocarcinoma), and HL-60 (human promyelocytic leukemia) cell lines. Compound 1 also showed antitumor activity on the life span of ICR mice intraperitoneally implanted with 1 x 10(6) cells of sarcoma 180.
––Lee YH, Park JD, Baek NI, Kim SI, Ahn BZ. Planta Med. 1995 Apr;61(2):178-80.