RESUMO
Gemcitabine (GEM) is a standard chemotherapeutic agent for patients with pancreatic cancer; however, GEM-based chemotherapy has a high rate of toxicity. A combination of GEM and active constituents from natural products may enhance its therapeutic efficacy and reduce its toxicity. This study investigated the synergistic effects of the combination of liriopesides B (LirB) from Liriope spicata var. prolifera and GEM on human pancreatic cancer cells. The results of our study showed that the combination of LirB and GEM synergistically decreased the viability of pancreatic cancer cells. The combination also caused a strong increase in apoptosis and a strong decrease in cell migration and invasion. Furthermore, LirB combined with GEM had potent inhibitory effects on pancreatic cancer stem cells (CSCs). Studies on the mechanisms of action showed that the combination more potently inhibited protein kinase B (Akt) and nuclear factor kappa B (NF-κB), as well as the downstream antiapoptotic molecules B-cell lymphoma 2 (Bcl-2) and survivin than either agent used alone. The results of this study suggest that the combination of LirB with GEM may improve the efficacy of GEM for the treatment of pancreatic cancer.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina/farmacologia , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , NF-kappa B/metabolismo , Apoptose , Proliferação de CélulasRESUMO
Two new patchoulene sesquiterpenoid glycosides (1-2), a natural patchoulane-type sesquiterpenoid (3) and a natural cadinene-type sesquiterpenoid (4), were isolated from the aerial parts of Pogostemon cablin (Blanco) Benth., together with eleven known sesquiterpenoids (5-15) and eleven known flavonoids (16-26). Their chemical structures were elucidated on the basis of spectroscopic methods, including NMR, HRESIMS, IR, and CD spectroscopic data analysis, as well as chemical hydrolysis. The isolated compounds 1-13 and 15-26 were tested for inhibitory effects on the proliferation of HepG2 cancer cells. Among them, compounds 17 and 19 displayed anti-proliferative effects against HepG2 cells with IC50 values of 25.59 and 2.30 µM, respectively. Furthermore, the flow cytometry analysis and Western blotting assays revealed that compound 19 significantly induced apoptosis of HepG2 cells by downregulating the ratio of Bcl-2/Bax and upregulating the expression of cleaved caspase-3 and cleaved caspase-9. Therefore, the potential pharmaceutical applications of P. cablin would be applied according to our study findings.
RESUMO
Cytokine-mediated inflammatory response is considered a cause of skin lesion in COVID-19 patients. Complanatuside is a flavonol glycoside isolated from Astragalus complanatus. Flavonoids from Astragalus complanatus were reported to have anti-inflammatory and anticancer activities but the potential protective effect of complanatuside on cytokine-induced inflammatory damage in skin keratinocytes is not known. The aim of this study is to explore the inhibitory effect of complanatuside on inflammation and its underlying mechanisms in skin epithelial HaCaT cells treated with inflammatory cytokines. The combination of IFN-γ, TNF-α, and IL-6 decreased cell viability, increased cell death, and pyroptosis in HaCaT cells. Treatment with complanatuside alleviated the effects of the cytokine combination on HaCaT cells. Complanatuside down-regulated pyroptosis related to NLRP3, GSDMD, and ASC. The effects of complanatuside were related to vast reductions in the levels of iNOS, COX-2, and ROS. Results of the present study indicate that complanatuside inhibited inflammation and protected the cells from inflammatory cell damage in HaCaT cells treated with the combination of IFN-γ, TNF-α, and IL-6. Complanatuside may be a promising candidate for inhibiting COVID-19 related skin inflammatory damage.
RESUMO
Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients.