Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells

Ma, Chaobing,Zu, Xueyin,Liu, Kangdong,Bode, Ann M.,Dong, Zigang,Liu, Zhenzhen,Kim, Dong Joon Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.9

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

Calculation of Magnetic Field for Cylindrical Stator Coils in Permanent Magnet Spherical Motor

Li, Hongfeng,Ma, Zigang,Han, Bing,Li, Bin,Li, Guidan The Korean Institute of Electrical Engineers 2018 Journal of Electrical Engineering & Technology Vol.13 No.6

This paper analyzed the magnetic field produced by the cylindrical stator coils of permanent magnet spherical motor (PMSM). The elliptic equations about the vector magnetic potential were given. Given that the eddy current effects are neglected, the magnet field of the PMSM is regarded as irrotational field, which can be calculated by scalar magnetic potential. The current density of cylindrical stator coil was proposed based on the definition of current density. The expression of current density of stator coil was obtained according to the double Fourier series decomposition and spherical harmonic functions. Then the magnetic flux density for scalar magnetic potential was derived. Further, the influence of different parameters on radial flux density was also analyzed. Finally, the results by the analytical method in this paper were validated by finite element analysis (FEA).

Calculation of Magnetic Field for Cylindrical Stator Coils in Permanent Magnet Spherical Motor

Hongfeng Li,Zigang Ma,Bing Han,Bin Li,Guidan Li 대한전기학회 2018 Journal of Electrical Engineering & Technology Vol.13 No.6

This paper analyzed the magnetic field produced by the cylindrical stator coils of permanent magnet spherical motor (PMSM). The elliptic equations about the vector magnetic potential were given. Given that the eddy current effects are neglected, the magnet field of the PMSM is regarded as irrotational field, which can be calculated by scalar magnetic potential. The current density of cylindrical stator coil was proposed based on the definition of current density. The expression of current density of stator coil was obtained according to the double Fourier series decomposition and spherical harmonic functions. Then the magnetic flux density for scalar magnetic potential was derived. Further, the influence of different parameters on radial flux density was also analyzed. Finally, the results by the analytical method in this paper were validated by finite element analysis (FEA).

Resveratrol directly targets COX-2 to inhibit carcinogenesis

Zykova, Tatyana A.,Zhu, Feng,Zhai, Xiuhong,Ma, Wei-Ya,Ermakova, Svetlana P.,Lee, Ki Won,Bode, Ann M.,Dong, Zigang Wiley Subscription Services, Inc., A Wiley Company 2008 Molecular carcinogenesis Vol.47 No.10

<P>Targeted molecular cancer therapies can potentially deliver treatment directly to a specific protein or gene to optimize efficacy and reduce adverse side effects often associated with traditional chemotherapy. Key oncoprotein and oncogene targets are rapidly being identified based on their expression, pathogenesis and clinical outcome. One such protein target is cyclooxygenase-2 (COX-2), which is highly expressed in various cancers. Research findings suggest that resveratrol (RSVL; 3,5,4′-trihydroxy-trans-stilbene) demonstrates nonselective COX-2 inhibition. We report herein that RSVL directly binds with COX-2 and this binding is absolutely required for RSVL's inhibition of the ability of human colon adenocarcinoma HT-29 cells to form colonies in soft agar. Binding of COX-2 with RSVL was compared with two RSVL analogues, 3,3′,4′,5′,5-pentahydroxy-trans-stilbene (RSVL-2) or 3,4′,5-trimethoxy-trans-stilbene (RSVL-3). The results indicated that COX-2 binds with RSVL-2 more strongly than with RSVL, but does not bind with RSVL-3. RSVL or RSVL-2, but not RSVL-3, inhibited COX-2-mediated PGE<SUB>2</SUB> production in vitro and ex vivo. HT-29 human colon adenocarcinoma cells express high levels of COX-2 and either RSVL or RSVL-2, but not RSVL-3, suppressed anchorage independent growth of these cells in soft agar. RSVL or RSVL-2 (not RSVL-3) suppressed growth of COX-2<SUP>+/+</SUP> cells by 60% or 80%, respectively. Notably, cells deficient in COX-2 were unresponsive to RSVL or RSVL-2. These data suggest that the anticancer effects of RSVL or RSLV-2 might be mediated directly through COX-2. © 2008 Wiley-Liss, Inc.</P>

Licochalcone A, a Natural Inhibitor of c-Jun <i>N</i>-Terminal Kinase 1

Yao, Ke,Chen, Hanyong,Lee, Mee-Hyun,Li, Haitao,Ma, Weiya,Peng, Cong,Song, Nu Ry,Lee, Ki Won,Bode, Ann M.,Dong, Ziming,Dong, Zigang American Association for Cancer Research 2014 Cancer Prevention Research Vol.7 No.1

<P>The c-<I>Jun N</I>-terminal kinases (JNK) play an important role in many physiologic processes induced by numerous stress signals. Each JNK protein appears to have a distinct function in cancer, diabetes, or Parkinson's disease. Herein, we found that licochalcone A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity but had little effect on JNK2 <I>in vitro</I> activity. Although licochalcone A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both <I>ex vivo</I> and <I>in vitro</I> systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expressed compared with normal cell lines. In cancer cell lines, treatment with licochalcone A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. The inhibition resulted in G<SUB>1</SUB> phase arrest and apoptosis. Moreover, an <I>in vivo</I> xenograft mouse study showed that licochalcone A treatment effectively suppressed the growth of HCT116 xenografts, without affecting the body weight of mice. These results show that licochalcone A is a selective JNK1 inhibitor. Therefore, we suggest that because of the critical role of JNK1 in colon cancer and pancreatic carcinogenesis, licochalcone A might have preventive or therapeutic potential against these devastating diseases. <I>Cancer Prev Res; 7(1); 139–49. ©2013 AACR</I>.</P>

Epigallocatechin gallate suppresses lung cancer cell growth through Ras-GTPase-activating protein SH3 domain-binding protein 1.

Shim, Jung-Hyun,Su, Zheng-Yuan,Chae, Jung-Il,Kim, Dong Joon,Zhu, Feng,Ma, Wei-Ya,Bode, Ann M,Yang, Chung S,Dong, Zigang American Association for Cancer Research, Inc 2010 Cancer prevention research Vol.3 No.5

<P>Green tea is a highly popular beverage globally. Green tea contains a number of polyphenol compounds referred to as catechins, and (-)-epigallocatechin gallate (EGCG) is believed to be the major biologically active compound found in green tea. EGCG has been reported to suppress lung cancer, but the molecular mechanisms of the inhibitory effects of EGCG are not clear. We found that EGCG interacted with the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) with high binding affinity (K(d) = 0.4 micromol/L). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells, which express much lower levels of G3BP1. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1 H1299 cells were resistant to the inhibitory effects of EGCG on growth and colony formation compared with shMock-transfected H1299 cells. EGCG interfered with the interaction of G3BP1 and the Ras-GTPase-activating protein and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1 downstream signaling, including extracellular signal-regulated kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, in wild-type H1299 and shMock H1299 cells but had little effect on H460 or shG3BP1 H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1.</P>