Combinatorial Antitumor Effect of Rapamycin andβ-Elemene in Follicular Thyroid Cancer Cells

Abstract

Background. mTOR signaling would be a promising target for thyroid cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in most cancer types was modest. A new focus on development of combinatorial strategies with rapalogs is increasing. Objective. Investigating the combinatorial antitumor effect of rapamycin and β-elemene in follicular thyroid cancer cells. Methods. MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/or β-elemene. To analyze their combinatorial effect, immunoblotting was performed to analyze the activation status of AKT. Moreover, β-elemene attenuated rapamycin-induced immunosuppression was tested in mice. Results. Combination of rapamycin and β-elemene exerted significant synergistic antiproliferative effects in FTC-133 cell lines in vitro, based on inhibiting the AKT feedback activation induced by rapamycin. In vivo, the β-elemene could attenuate rapamycin-induced immunosuppression via reversing imbalance of Treg/Th17, with the underlying mechanism needed to be declared. Conclusions. We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

Cytotoxic Essential Oils from Eryngium campestre and Eryngium amethystinum (Apiaceae) Growing in Central Italy

“…It was capable of arresting proliferation in the lymphocytes and to induce apoptosis by a caspase-3 independent pathway. [40] b-Elemene is a sesquiterpene widely occurring in nature and used to treat a variety of tumors [41] to potentiate the antitumor effect of conventional drugs, [42] and to reverse the multidrug resistance in cancer. [43] In addition, b-elemene proved to be highly effective as larvicidal against the mosquitoes Anopheles subpictus, Aedes albopictus, and Culex tritaeniorhynchus and safe against the non-target fish Gambusia affinis.…”

“…It differs from aromadendrene only in the configuration at the C(1) position. [40] b-Elemene is a sesquiterpene widely occurring in nature and used to treat a variety of tumors [41] to potentiate the antitumor effect of conventional drugs, [42] and to reverse the multidrug resistance in cancer. [35] Oxygenated derivatives of allo-aromadendrene proved to be fungitoxic against Cladosporium cladosporioides and C. sphaerospermum.…”

Evaluation of the efficacy and safety of elemene in treating malignant pleural effusion caused by tumors

“…Elemene has been widely used in the treatment of cancer, including complications of cancer. [ 59 ] In recent years, several publications supporting elemene in the treatment of malignant pleural effusion have been reported, but their findings are established based on limited number of patients. [ 8 , 12 ] In this meta-analysis, we found that elemene could significantly improve the short-term control of malignant pleural effusion.…”

Drug delivery systems for elemene, its main active ingredient β-elemene, and its derivatives in cancer therapy

“…Sun et al 100 synthesized a β-elemene monosubstituted amine derivative (4a) and a Re(CO) 3 -β-elemene derivative (13). In vitro antiproliferative activity in HeLa cells was significantly improved through reduction of Rb phosphorylation and cyclin D1 protein level.…”

“…3 Chemotherapeutic drugs, such as 5-fluorouracil, temozolomide (TMZ), cisplatin, gefitinib, endostar, etoposide, rapamycin, oxaliplatin, taxanes, and ligustrazine, as well as radiotherapy and hyperthermia, could improve the antitumor effects and reverse multiple-drug resistance (MDR) in combination with β-elemene. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] In recent years, the study of mechanism of action of β-elemene has made great progress. β-elemene exerts its effects by modulating multiple molecular targets.…”