cytellin and Lung-Neoplasms

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for "cancer cell specific" therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.

Topics: Apoptosis; Breast Neoplasms; Cell Cycle; Colonic Neoplasms; Dietary Supplements; Drug Delivery Systems; Female; Humans; Leukemia; Liposomes; Lung Neoplasms; Male; Neoplasms; Orphan Drug Production; Phytoestrogens; Prostatic Neoplasms; Signal Transduction; Sitosterols

Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and β-sitosterol.. In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.. Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).. Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.. F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

Topics: Acanthaceae; Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Female; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Lutein; Mice, Inbred BALB C; Plant Extracts; Sitosterols; Splenic Neoplasms; Tumor Burden

Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA‑BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted. The reduced punctate accumulations of GFP-LC3 were detected in pcDNA-BAMBI and β-sitosterol groups, especially in pcDNA-BAMBI + β-sitosterol group. BAMBI overexpression and β-sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in A549 cells. In addition, the levels of transforming growth factor-β (TGF‑β)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-β overexpression further confirmed that BAMBI overexpression and β-sitosterol treatment suppre-ssed autohagy and viability of A549 cells was through TGF-β/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI toge-ther with β-sitosterol. These results indicate that BAMBI overexpression and β-sitosterol may serve as novel targets for the treatment of NSCLC.

Topics: A549 Cells; Animals; Autophagy; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Genetic Vectors; Humans; Lung Neoplasms; Membrane Proteins; Mice; Signal Transduction; Sitosterols; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta; Up-Regulation

To study the isolation and characterization of the constituent responsible for the cytotoxic activity of the ethanolic extract of stem of Capparis decidua (C. decidua).. The preliminary cytotoxic effect of isolated compound (β-Sitosterol triacontenate) was investigated by MTT assay on A549 solid tumor cells.. IC(50) value of the β-Sitosterol triacontenate was found to be 1 μM. The cytotoxic activity increased in a dose dependent manner in case of β-Sitosterol triacontenate.. The data therefore provide direct evidence for the role of β-Sitosterol triacontenate as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant cells.

Topics: Antineoplastic Agents; Capparis; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Neoplasm Invasiveness; Neoplasm Metastasis; Plant Extracts; Plant Stems; Sitosterols

Two new diterpenoids, 14,18-dihydroxyabieta-8,11,13-trien-7-one (1) and 13-acetyl-14,18-dihydroxy-podocarpa-8,11,13-triene (2), together with eight known compounds, i.e., gaultheric acid (3), vanillic acid (4), 4-hydroxybenzoic acid (5), cinnamic acid (6), stearic acid (7), palmitic acid (8), beta-sitosterol (9), and stigmasterol (10), were isolated from the MeOH extract of the whole plant of Gaultheria itoana Hayata (Ericaceae). The structures of the new constituents were elucidated by spectroscopic methods (UV, IR, and 1D- and 2D-NMR) and by mass spectrometry (HR-ESI-MS). Among them, 1 and 2 were demonstrated to exhibit significant cytotoxic activity against the LNCaP cell line.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cinnamates; Diterpenes; Gaultheria; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Methanol; Molecular Structure; Palmitic Acid; Parabens; Plant Extracts; Sitosterols; Spectrometry, Mass, Electrospray Ionization; Stearic Acids; Stigmasterol; Vanillic Acid

To investigate chemopreventive effect of liposomal beta-sitosterol on tumor metastasis, we prepared liposomal beta-sitosterol composed of egg yolk phosphatidylcholine for oral delivery. Although orally administered beta-sitosterol (4 micromol as beta-sitosterol/mouse) was not absorbed into plasma, the amount of immune response cytokines such as IL-12 and IL-18 was increased in the small intestine after the liposome intake. Moreover, after daily oral administration of the liposome for 7 d, natural killer (NK) cell activity in the mice was increased, suggesting that the immune surveillance activity of mice was enhanced by the liposomal beta-sitosterol intake. Thus, we examined metastatic potential of B16BL6 melanoma cells, which were intravenously injected into mice after sequential administration of liposomal beta-sitosterol for 7 d. The number of metastatic colonies in the lungs was significantly less than that of control group two weeks after the injections of the cells. These results suggest that daily liposomal beta-sitosterol intake prevents tumor metastasis may be due to enhancement of gut immune surveillance systems.

Topics: Animals; Antineoplastic Agents; Interleukin-12; Interleukin-18; Intestine, Small; Killer Cells, Natural; Liposomes; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Sitosterols; Tissue Distribution