Antitumor activity of Koningic acid in thyroid cancer by inhibiting cellular glycolysis.

PURPOSE: Koningic acid (KA), a sesquiterpene lactone, has been identified as an antimicrobial agent. Recent studies have revealed KA's antitumor activities in colorectal cancer, leukemia, and lung cancer. However, its antitumor effect in thyroid cancer remains largely unknown. METHODS: The effects of KA on proliferation, colony formation, apoptosis in thyroid cancer cells were assessed by MTT assay and flow cytometry. After KA treatment, the glycolysis ability of thyroid cancer cells was detected by ECAR, and the glycolytic products and relative ATP levels were measured by ELISA. The underlying mechanisms of antineoplastic activity of KA in thyroid cancer were detected by Western blot. Finally, the antineoplastic activity in vivo was observed in Xenograft mouse models. RESULTS: KA inhibited the proliferation, colony formation, and increased cell apoptosis in thyroid cancer cell lines in a dose and time-dependent manner. We verified that the glycolysis ability, ATP production, and lactic acid level in thyroid cancer cells had experienced an extensive decrease after KA treatment. In addition, lactic acid, the metabolite of glycolysis, could weaken the effect of KA on its colony formation ability in C643 thyroid cancer cell line. Our data also showed that KA kills thyroid cancer cells by inhibiting the MAPK/ERK pathway and decreasing Bcl-2 level. By contrast with the control group, the growth of xenograft tumor was dramatically inhibited by KA without obvious drug side effects. CONCLUSION: Our data demonstrate that KA kills thyroid cancer cell lines by inhibiting their glycolysis ability, the MAPK/ERK pathway and the Bcl-2 level and suggest that KA has potential clinical value in thyroid cancer therapy.

Disruption of Cigarette Smoking Addiction After Dorsal Striatum Damage.

Studies have shown that addictive behavior is associated with many brain regions, such as the insula, globus pallidus, amygdala, nucleus accumbens, and midbrain dopamine system, but only a few studies have explored the role of the dorsal striatum in addictive behavior. In June 2020, we started contacting 608 patients who were hospitalized between January 2017 and December 2019, and we recruited 11 smoking addicts with dorsal striatum damage and 20 controls with brain damage that did not involve the dorsal striatum (the damaged areas included the frontal lobe, temporal lobe, parietal lobe, brain stem, thalamus, internal capsule, and so on). All study participants had brain damage due to acute cerebral infarction. Disruption of smoking addiction was found to be significantly associated with the dorsal striatum (Phi = 0.794770, P = 0.000015). Our findings suggested that patients in the dorsal striatum group were more likely to discontinue smoking than those in the non-dorsal striatum group. The characteristics of this interruption is that smoking can be quit more easily and quickly without recurrence and that the impulse to smoke is reduced. These results suggest that the dorsal striatum is a key area for addiction to smoking.

Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is a rare malignancy and has a very poor prognosis due to its aggressive behavior and resistance to treatment. No effective treatment modalities are currently available. Lenvatinib has shown encouraging results in the patients with radioiodine-refractory differentiated thyroid cancer (DTC); however, lenvatinib monotherapy has a relatively low efficacy against ATC. In this study, we assessed the antitumor effects of a combination of lenvatinib and microtubule inhibitor paclitaxel in ATC cells in vitro and in vivo. Our data showed that lenvatinib monotherapy was less effective than paclitaxel monotherapy in ATC cell lines and xenografts. The addition of lenvatinib to paclitaxel synergistically inhibited colony formation and tumor growth in nude mice, and induced G2/M phase cell cycle arrest and cell apoptosis as compared to lenvatinib or paclitaxel monotherapy. Taken together, this is the first study to suggest that lenvatinib/paclitaxel combination may be a promising candidate therapeutic strategy for ATC.