Inhibition of lung cancer in diethylnitrosamine‐induced mice by Rhizoma paridis saponins

Abstract

Lung cancer is the foremost cause of cancer mortality and a growing economic burden worldwide. Rhizoma paridis saponins (RPS) have been reported to exhibit potential anti-tumor effects on many kinds of tumor models. The present study was designed to investigate the mechanism-based chemopreventive nature of RPS against DEN-induced lung carcinogenesis in Kunming mice. As a result, the treatment with RPS reduced the severity of pulmonary histopathology. The mechanism of its antitumor effect involved in (a) reducing oxidative stress injury through up-regulating activities of CAT and SOD; (b) down-regulating the levels of inflammatory factors, like TNF-α, IL6, COX-2, and PGE2; (c) activation of caspase-3 and up-regulating the pro-apoptotic protein Bax; (d) decreasing the expression of PCNA; (e) depressing the expression of cancer stem cells marker CD133; (f) suppressing aberrant expression of cytokeratin 8 and 18; and (g) inhibiting EGFR/ PI3 K/Akt, EGFR/Ras/Erk and NF-κB pathways. Taken together, RPS would be a potent agent inhibiting lung tumor in the future.

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Lung Cancer

“…In our study, JNK and COX-2 mRNA in lung tissue and TNF-α and IL-1β protein levels in serum increased in animals as a result of DEN administration. Studies on lung tissue and serum demonstrate that DEN treatment increased COX-2, TNF-α, and IL-1β levels [30,31]. To the best of our knowledge, the results of the present study were rst demonstrating that DEN leads to high level of JNK expression in lung tissue.…”

Chemical Constituents and Pharmacological Activities of Steroid Saponins Isolated from Rhizoma Paridis

“…A number of studies have also examined the PS in lung cancer models. In DEN-induced mouse lung cancer, polyphyllin D, pb/formosanin C, dioscin, polyphyllin V, polyphyllin VI, polyphyllin VII, Paris saponin H, and gracillin displayed significant inhibitory effects on tumor development and growth, and the possible mechanism was due to reduction of the expression levels of TNF-α, IL-6, COX-2, PGE2, CK8, and CK18 and inactivation of the EGFR/PI3K/ Akt, EGFR/Ras/Erk, and NF-κB pathways [15]. In the LA795 cellular and xenograft model, polyphyllin D, pb/formosanin C, dioscin, Paris saponin H, and polyphyllin VII were also shown to have significant antitumor activity by inducing apoptosis and blocking the migration [31].…”

“…In particular, the antitumor pharmacological activity of Rhizoma Paridis extracts has emerged a major focus of research. Recent several years, polyphylla saponins have been widely reported to inhibit tumor growth in cancer of the breast [13], liver [14], lung [15], ovary [16], and colon [17], as well as other types of malignancy. All these findings bring lights to the discovery of new drugs for cancer.…”

Relationship between Lung Carcinogenesis and Chronic Inflammation in Rodents

“…Tobacco smoke includes many carcinogens, such as PAH, N-Nitrosamines including NNK, aza-arenes, aromatic amines, heterocyclic amines, aldehydes, miscellaneous organic compounds, and inorganic compounds [28]. N-nitrosodiethylamine (DEN) an N-Nitrosoamine [29][30][31], and benzo[a]pyrene (BaP), a PAH [32,33], are well-known carcinogens in tobacco smoke and induce carcinoma in almost all human tissues, including the lungs, mouth, throat, larynx, esophagus, stomach, colon, kidneys, liver, pancreas, cervix, bladder, and blood. However, tobacco smoke inhalation assays in laboratory animals show low incidence of pulmonary tumor formation, and most of the tumors are adenomas with the occasional adenocarcinoma as opposed to the highly invasive squamous cell carcinoma seen in human smokers [34].…”