Prostate cancer is one of the most common cancers among men. Currently available therapies improve patient survival against local prostate cancer but have shown severe side effects. Advanced prostate cancer is still incurable. Studies have suggested the involvement of non-coding RNAs, especially micro-RNAs (miRNAs), in the regulation of multiple cellular events in cancer and thus several clinical trials are ongoing using miRNAs mimics or inhibitors. We previously demonstrated that miRNA-29b-3p (miR-29b) was downregulated in prostate cancer and that the overexpression of miR-29b limited prostate cancer metastasis. However, the therapeutic potential of the miR-29b against prostate cancer remains unknown. Here, we evaluated the therapeutic role of miR-29b in in vivo prostate tumors in a mouse model. Intratumoral injection of mimic miR-29b significantly inhibited prostate cancer xenograft tumor growth in nude mice. Subsequent study demonstrated that the overexpression of miR-29b reduced prostate cancer cell PC3 proliferation in a time dependent manner and induced cell death. Mechanistic study using a cancer pathway specific transcriptomic array revealed a significant overexpression of the pro-apoptotic gene BCL2L11 (Bim) in the miR-29b overexpressed PC3 cells, which was further verified in PC3 cells overexpressing miR-29b. We also observed a significant induction of Bim protein in miR-29b treated xenograft tumors. The induction of cytosolic accumulation of cytochrome C and PARP cleavage in miR-29b overexpressed PC3 cells was observed. Thus, our results suggest that miR-29b can be used as a potential molecule for prostate cancer therapy.

Cancer is the second leading cause of death worldwide. Many dietary plant products show promising anticancer effects. Bitter melon or bitter gourd (Momordica charantia) is a nutrient-rich medicinal plant cultivated in tropical and subtropical regions of many countries. Traditionally, bitter melon is used as a folk medicine and contains many bioactive components including triterpenoids, triterpene glycoside, phenolic acids, flavonoids, lectins, sterols and proteins that show potential anticancer activity without significant side effects. The preventive and therapeutic effects of crude extract or isolated components are studied in cell line-based models and animal models of multiple types of cancer. In the present review, we summarize recent progress in testing the cancer preventive and therapeutic activity of bitter melon with a focus on underlying molecular mechanisms. The crude extract and its components prevent many types of cancers by enhancing reactive oxygen species generation; inhibiting cancer cell cycle, cell signaling, cancer stem cells, glucose and lipid metabolism, invasion, metastasis, hypoxia, and angiogenesis; inducing apoptosis and autophagy cell death, and enhancing the immune defense. Thus, bitter melon may serve as a promising cancer preventive and therapeutic agent.

SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from COVID-19 patients’ plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C–C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ.

Background: Metabolic reprogramming is one of the hallmarks of cancer which favours rapid energy production, biosynthetic capabilities and therapy resistance. In our previous study, we showed bitter melon extract (BME) prevents carcinogen induced mouse oral cancer. RNA sequence analysis from mouse tongue revealed a significant modulation in “Metabolic Process” by altering glycolysis and lipid metabolic pathways in BME fed group as compared to cancer group. In present study, we evaluated the effect of BME on glycolysis and lipid metabolism pathways in human oral cancer cells. Methods: Cal27 and JHU022 cells were treated with BME. RNA and protein expression were analysed for modulation of glycolytic and lipogenesis genes by quantitative real-time PCR, western blot analyses and immunofluorescence. Lactate and pyruvate level was determined by GC/MS. Extracellular acidification and glycolytic rate were measured using the Seahorse XF analyser. Shotgun lipidomics in Cal27 and JHU022 cell lines following BME treatment was performed by ESI/ MS. ROS was measured by FACS. Results: Treatment with BME on oral cancer cell lines significantly reduced mRNA and protein expression levels of key glycolytic genes SLC2A1 (GLUT-1), PFKP, LDHA, PKM and PDK3. Pyruvate and lactate levels and glycolysis rate were reduced in oral cancer cells following BME treatment. In lipogenesis pathway, we observed a significant reduction of genes involves in fatty acid biogenesis, ACLY, ACC1 and FASN, at the mRNA and protein levels following BME treatment. Further, BME treatment significantly reduced phosphatidylcholine, phosphatidylethanolamine, and plasmenylethanolamine, and reduced iPLA2 activity. Additionally, BME treatment inhibited lipid raft marker flotillin expression and altered its subcellular localization. ER-stress associated CHOP expression and generation of mitochondrial reactive oxygen species were induced by BME, which facilitated apoptosis. Conclusion: Our study revealed that bitter melon extract inhibits glycolysis and lipid metabolism and induces ER and oxidative stress-mediated cell death in oral cancer. Thus, BME-mediated metabolic reprogramming of oral cancer cells will have important preventive and therapeutic implications along with conventional therapies. Graphical