Anti-Cancer Effects of CDK4/6 Inhibitor LEE011 and Chemotherapy Drugs on Lymphocytic Leukemia L1210 Cells.

BACKGROUND/AIM: Chronic lymphocytic leukemia is a slowly-progressing disease in which symptoms often do not manifest until years after disease onset. In advanced stages, infection and bleeding are common. Past studies have shown that the interaction between CDK4/6 inhibitors and chemotherapy drugs can enhance the anti-tumor efficacy of drugs and limit toxicity. Therefore, in this study, the treatment effects of combining the CDK4/6 inhibitor LEE011 with chemotherapy drugs bendamustine or hydroxyurea were investigated in vitro. MATERIALS AND METHODS: The mouse lymphocytic leukemia cell line L1210 was treated with LEE011 combined with hydroxyurea or bendamustine. Western blot and flow cytometry were performed to elucidate the mechanisms behind tumor suppression. RESULTS: LEE011 combined with hydroxyurea or bendamustine significantly inhibited proliferation of L1210 cell lines in a concentration- and time-dependent manner as well as increased the arrest of cells in G1 and S phases. The combination of LEE011 with hydroxyurea also reduced the phosphorylation of Rb while increased the expression of total Rb protein. Furthermore, reduced expression of GPX4, which is a key protein in ferroptosis, indicates that the tumor suppression effects of this drug combination could involve ferroptosis. CONCLUSION: CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.

Hinokitiol Inhibits the Viability of Oral Squamous Carcinoma Cells by Inducing Apoptosis and Autophagy.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide, per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of hinokitiol on cell viability in OSCC cells. MATERIALS AND METHODS: The anticancer effect and mechanism of action of hinokitiol in OSCC cells were analyzed by cell viability assays and cell cycle analysis using flow cytometry, while apoptosis and autophagy-related protein expression was measured using western blot. RESULTS: The results showed that hinokitiol concentration-dependently reduced the viability of SCC4 and SCC25 cells by downregulating the levels of cell-cycle mediators, such as cyclin B1, cyclin D1 and cyclin-dependent kinase-1 (CDK1). Furthermore, hinokitiol promoted apoptosis in SCC25 cells based on the presence of active cleaved caspase-3. Hinokitiol also induced autophagy by promoting the accumulation of the microtubule-associated protein light chain 3B (LC3B) and the expression of the sequestosome-1 (p62/SQSTM). CONCLUSION: Hinokitiol exhibits anti-proliferation activity and has pro-apoptotic effects on OSCC cell lines.

New silky lacewings from mid-Cretaceous Burmese amber (Insecta: Neuroptera: Psychopsidae).

A new genus with a new species, Lasiopsychops impunctatus gen. et sp. nov., and a new species, Electropsychops oligophlebius sp. nov., of silky lacewings in Psychopsidae are described from mid-Cretaceous Burmese amber. Lasiopsychops gen. nov. has typical characters of the extant Psychopsidae, i.e., broad triangular forewing, broad costal space, presence of the vena triplica and the paired ectoprocts and gonocoxites 9 of female genitalia, implying its close affinity with the extant lineages of Psychopsidae. The new findings of the Cretaceous psychopsids enhance our knowledge on the diversity and evolution of Psychopsidae during the Mesozoic.

Expression and clinical significance of cyclooxygenase-2 and interleukin-32 in primary gastric B-cell lymphoma.

Cyclooxygenase-2 (COX-2) and interleukin-32 (IL-32) expression has been examined in various carcinomas and inflammations, and has been suggested to be significant in tumor progression and prognosis. The present study was conducted to investigate the expression of COX-2 and IL-32 in primary gastric B-cell lymphoma in order to define their clinical significance and their association with Helicobacter pylori (Hp) infection. COX-2 and IL-32 protein expression was detected in 31 primary gastric B-cell lymphoma patients and 19 chronic gastritis patients with immunohistochemistry. COX-2 and IL-32 expression was significantly higher in primary gastric lymphoma (PGL) tissues compared with gastritis tissues (51.6 vs. 21.1% for COX-2, P=0.032; and 58.1 vs. 26.3% for IL-32, P=0.029) and was significantly higher in Hp+ lymphoma tissues compared with Hp- lymphoma tissues (66.7 vs. 20% for COX-2, P=0.015; and 71.4 vs. 30% for IL-32, P=0.029). In the PGL tissues, the expression level of COX-2 was positively correlated with the expression level of IL-32, and the two were each positively correlated with Hp infection (P=0.004 for COX-2 and IL-32; P=0.01 for COX-2 and Hp infection; and P=0.003 for IL-32 and Hp infection). COX-2 expression was found to be significantly associated (P<0.05) with an aggressive tumor type, higher expression of Ki-67, frequent lymph node metastasis and advanced stage. IL-32 expression was found to be significantly correlated (P<0.05) with frequent lymph node metastasis and an advanced stage. The survival time was longer in the COX-2- and IL-32- lymphoma patients compared with the COX-2+ and IL-32+ lymphoma patients, but these differences were not statistically significant. These results suggested that Hp infection and the expression of COX-2 and IL-32 were closely linked with each other, and that the overexpression of COX-2 and IL-32 was correlated with tumor progression in primary gastric B-cell lymphoma, thus indicating potential novel therapeutic target.