Natural products are a precious source of promising leads for the development of novel cancer therapeutics. Recently, triterpenoids in Alismatis rhizoma has been widely demonstrated for their anti-cancer activities in cancer cells. In this study, we examined the inhibitory effects of alisol A in human breast cancer cells. We demonstrated that alisol A exhibited significant anti-proliferative effects in MDA-MB-231 cells and this response was related to autophagy induction. Alisol A-induced autophagy was supported by the triggered autophagosome formation and increased LC3-II levels. Interestingly, autophagy inhibitor 3-MA significantly reversed the cytotoxic effects induced by alisol A. Meanwhile, alisol A-induced autophagy was significantly inhibited by 3-MA in MDA-MB-231 cells. Cell cycle analysis revealed that alisol A arrested the cell cycle at G0/G1 phase. The expression level of cell cycle regulatory proteins cyclin D1 was significantly down regulated. In addition, the suppression of NF-κB and PI3K/Akt/mTOR pathways in MDA-MB-231 cells was observed. Furthermore, alisol A significantly suppressed the migration and invasion of MDA-MB-231 cells by inhibiting the expression levels of MMP-2 and MMP-9. Taken together, our results demonstrated that alisol A could inhibit the proliferation and metastasis of MDA-MB-231 cells. It could be a promising agent for breast cancer therapy.
Exosomes are cup-shaped extracellular small nanovesicles, with a diameter ranging from 30 to 100 nm, and composed of a phospholipid bilayer containing membrane proteins. 1 Exosomes are released into the extracellular compartment that comprises a large panel of proteins, mRNAs and regulatory microRNAs, directly shuttling the bioactive molecules among recipient cells. 2 The role of exosomes has been figured out in cancer, contributing to tumour growth, angiogenesis, escaping from the immune response, causing tumour cell migration and stimulating invasion of normal cells. 3 Most cells release exosomes, including cancer cells and populations that can associate with tumour tissue, such as heterogeneous MSCs. 4 MSCs are believed to have antitumour effects and mediate their therapeutic functions in a paracrine, rather than a cellular, manner. Growing evidence suggests that MSC-derived exosomes could transfer proteins
-Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose-and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of γH2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.
Although the curative effect of hematological malignancies has been improved in recent years, relapse or drug resistance of hematological malignancies will eventually recur. Furthermore, the microenvironment disorder is an important mechanism in the pathogenesis of hematological malignancies. Immunogenic cell death (ICD) is a unique mechanism of regulated cell death (RCD) that triggers an intact antigen‐specific adaptive immune response by firing a set of danger signals or damage‐associated molecular patterns (DAMPs), which is an immunotherapeutic modality with the potential for the treatment of hematological malignancies. This review summarizes the existing knowledge about the induction of ICD in hematological malignancies and the current research on combining ICD inducers with other treatment strategies for hematological malignancies.
Expansins, which are important components of plant cell walls, act as loosening factors to directly induce turgor-driven cell wall expansion, regulate the growth and development of roots, leaves, fruits, and other plant organs, and function essentially under environmental stresses. In multiple species, many expansin genes (EXPs) have been cloned and functionally validated but little is known in pomegranate. In this study, a total of 33 PgEXPs were screened from the whole genome data of ‘Taishanhong’ pomegranate, belonging to the EXPA(25), EXPB(5), EXLA(1), and EXLB(2) subfamilies. Subsequently, the composition and characteristics were analyzed. Members of the same branch shared similar motif compositions and gene structures, implying they had similar biological functions. According to cis-acting element analysis, PgEXPs contained many light and hormone response elements in promoter regions. Analysis of RNA-seq data and protein interaction network indicated that PgEXP26 had relatively higher transcription levels in all pomegranate tissues and might be involved in pectin lyase protein synthesis, whilst PgEXP5 and PgEXP31 might be involved in the production of enzymes associated with cell wall formation. Quantitative real-time PCR (qRT-PCR) results revealed that PgEXP expression levels in fruit peels varied considerably across fruit developmental phases. PgEXP23 was expressed highly in the later stages of fruit development, suggesting that PgEXP23 was essential in fruit ripening. On the other hand, the PgEXP28 expression level was minimal or non-detected. Our work laid a foundation for further investigation into pomegranate expansin gene functions.
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