Browsing by Subject "autophagy"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item Akt Isoforms: A Family Affair in Breast Cancer(MDPI, 2021-07-09) Basu, Alakananda; Lambring, Christoffer B.Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBalpha), Akt2(PKBbeta) and Akt3(PKBgamma). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer.Item Effects of Exercise Training on the Autophagy-Related Muscular Proteins Expression in Ovariectomized Rats(Frontiers Media S.A., 2019-06-13) Zhong, Weiquan; Shi, Xiangrong; Yuan, Honghua; Bu, Huimin; Wu, Lianlian; Wang, RenweiOvariectomy disrupts estrogen production and homeostasis. However, whether exercise training (ET) could counteract the ovariectomy-induced effect on muscular autophagy has remained elusive. This study examined muscular autophagy in ovariectomized (OVX) rats following 8 weeks of swimming ET. Here, 40 6-month-old female Sprague-Dawley rats were randomly divided into five groups: sham-operated control (Sham), OVX control (OVX), OVX with 60-min ET (OVX-60ET), 90-min ET (OVX-90ET), and 120-min ET (OVX-120ET) for 6 days/week. According to the results of Western blotting, the expression levels of autophagy-related proteins in the OVX gastrocnemius muscle, including mammalian target of rapamycin, uncoordinated 51-like kinase 1, Beclin-1, autophagy-related gene (Atg-7), and microtubule-associated protein light chains 3 were significantly decreased (all P < 0.05), while there was an elevation on the p62 level. ET appreciably mitigated the OVX-induced negative effects on muscle quality and the autophagy pathway, which seemed to be dependent on ET volume. The most optimal outcomes were observed in the OVX-90ET group. The OVX-120 group had an adversely augmented catabolic process associated with gastrocnemius muscle atrophy. In conclusion, the expression levels of autophagy proteins are decreased in OVX rats, which can be appreciably mitigated following 8 weeks of swimming ET.Item Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells(Spandidos Publications, 2020-06-19) Amaral de Mascena Costa, Luciana; Debnath, Dipti; Harmon, Ashlyn C.; de Sousa Araujo, Silvany; Diogenes da Silva Souza, Helivaldo; Filgueiras de Athayde Filho, Petronio; Wischral, Aurea; Adriao Gomes Filho, Manoel; Mathis, J. MichaelIn the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC50 value of MIH 2.4Bl was determined to be 45.8+/-0.8 microM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change >/=2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.Item Regulation of Autophagy by Protein Kinase C-epsilon in Breast Cancer Cells(MDPI, 2020-06-15) Basu, AlakanandaProtein kinase C-ɛ (PKCɛ), an anti-apoptotic protein, plays critical roles in breast cancer development and progression. Although autophagy is an important survival mechanism, it is not known if PKCɛ regulates autophagy in breast cancer cells. We have shown that silencing of PKCɛ by siRNA inhibited basal and starvation-induced autophagy in T47D breast cancer cells as determined by the decrease in LC3-II, increase in p62, and decrease in autophagy puncta both in the presence and absence of bafilomycin A1. The mechanistic target of rapamycin (mTOR) associates with Raptor or Rictor to form complex-1 (mTORC1) or complex-2 (mTORC2), respectively. Knockdown of PKCɛ attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKCɛ in MCF-7 cells caused activation of mTORC1 and an increase in LC3-I, LC3-II, and p62. The mTORC1 inhibitor rapamycin abolished the increase in LC3-I and p62. Knockdown of mTOR and Rictor or starvation enhanced autophagy in PKCɛ overexpressing cells. While overexpression of PKCɛ in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-ɑ. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKCɛ-overexpressing cells. Thus, PKCɛ promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy.