curcumin and Small-Cell-Lung-Carcinoma

Oral medication is the most acceptable therapy to treat chronic diseases. Natural drugs and excipients have unique advantages, such as low cost and high safety. We first investigated modified ethanol nanosomes for tumor treatment

Topics: Animals; Antineoplastic Agents; Biological Products; Cell Line, Tumor; Chitosan; Curcumin; Ethanol; Humans; Mice; Nanocomposites; Serum Albumin; Small Cell Lung Carcinoma; Xenograft Model Antitumor Assays

Oral administration shows good tolerance in patients. Botanic anticancer drugs without serious side effects have attracted increased attention worldwide. However, oral delivery of natural anticancer drugs faces great challenges due to low solubility, gastrointestinal side effects, first-pass effects, and P-glycoprotein efflux. Here, we loaded the natural polyphenol curcumin (Cc) into natural polysaccharide-cloaked lipidic nanocarriers (Cc@CLNs) to improve the efficacy in small-cell lung cancer (SCLC) associated with oral administration. Compared to other nanoformulations, Cc@CLNs have advantages of simple operation, easy scale-up, low cost, and high safety. Cc@CLNs improve bioavailability by inducing synergistic effects (efficient cell membrane penetration, inherent muco-adhesiveness, resistance to pepsin and trypsin degradation, promoted dissolution, enhanced epithelia/M cellular uptake and inhibition of efflux transporters) and countering the tendency of nanocarriers to aggregate and fuse, which limit lipid-based nanosystems. In this study, we first evaluated the oral bioavailability of Cc@CLNs in rats and their efficacy in H446 tumor-bearing mice. The oral bioavailability increased by 8.94-fold, and the tumor growth inhibition rate doubled compared to that achieved with free Cc. We investigated the action of Cc against SCLC stem cells, and Cc@CLNs greatly enhanced this action. The expression of CD133 and ABCG2 in the Cc@CLNs group decreased by 38.05% and 32.57%, respectively, compared to the respective expression levels in the control.

Topics: Administration, Oral; Animals; Biological Products; Cell Line, Tumor; Curcumin; Drug Carriers; Humans; Lipids; Mice; Nanoparticles; Polyphenols; Polysaccharides; Rats; Small Cell Lung Carcinoma; Xenograft Model Antitumor Assays

Curcumin (diferuloylmethane), an active component of the spice turmeric, induces apoptosis in several types of malignancies. However, little is known about its anticancer activity in small cell lung cancer (SCLC). SCLC represents a highly malignant and particularly aggressive form of cancer, with early and widespread metastases and a poor prognosis. In this study, we found that curcumin does not activate caspase-8 cleavage or alter the expression of apoptotic receptors FAS and TRAIL in NCI-H446 cells, suggesting that curcumin-induced apoptosis is not associated with death receptor-mediated pathways in these cells. Instead, curcumin caused apoptosis by increasing Bax expression while decreasing the expression of Bcl-2 and Bcl-xL. Curcumin induced a rapid decrease in mitochondrial membrane potential and the release of cytochrome c into the cytosol, followed by activation of caspase-9 and caspase-3. In addition, curcumin-induced apoptosis was accompanied by an increase of intracellular reactive oxygen species (ROS) level. These results indicated that a ROS-mediated mitochondrial pathway played an important role in the process of curcumin-induced apoptosis of human SCLC NCI-H446 cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Curcumin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Microscopy, Electron, Transmission; Mitochondria; Reactive Oxygen Species; Receptors, Death Domain; Signal Transduction; Small Cell Lung Carcinoma

Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1). Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and provide novel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC.

Topics: Antineoplastic Agents; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Cyclin B1; Humans; Interleukin-6; Janus Kinases; Lung Neoplasms; Matrix Metalloproteinases; Neovascularization, Pathologic; RNA Interference; Signal Transduction; Small Cell Lung Carcinoma; STAT3 Transcription Factor