Physalin B inhibits cell proliferation and induces apoptosis in undifferentiated human gastric cancer HGC‐27 cells

Abstract

Background Physalin B (PB) from Physalis angulata L. (Solanaceae) is a naturally occurring secosteroid with multiple biological activities, including anti‐inflammatory and anticancer activity. However, PB's effects and mechanisms in human gastric cancer (GC) cells are not well characterized. Methods The undifferentiated GC cell line HGC‐27 and semi‐differentiated GC cell line SGC‐7901 were treated with PB. Cell counting kit‐8 (CCK‐8) and colony formation assays were performed to evaluate cell viability. Apoptosis and the cell cycle were assessed by Annexin V/PI and PI/RNase DNA staining assays, respectively, and Western blotting was used to evaluate the expression of a protein. Results PB significantly inhibited the proliferation of HGC‐27 cells in a dose‐ and time‐dependent manner. Moreover, PB induced G0/G1 cycle arrest and caspase‐dependent apoptosis of HGC‐27 cells. Cleaved caspases 8, 3, and 7, poly(ADP)‐ribose polymerase (PARP), and the cyclin‐dependent kinase (CDK) inhibitor p‐Chk2 was induced by PB in HGC‐27 cells, while the cell cycle‐related proteins cyclin D1, cyclin D3, CDK4, CDK6, cyclin E, and phosphorylated retinoblastoma tumor suppressor protein (p‐Rb) were downregulated in a dose‐dependent manner. Conclusions PB inhibits proliferation via cyclin‐dependent kinase and induces caspase‐dependent apoptosis in HGC‐27 cells, suggesting that PB might be a novel and effective agent for undifferentiated GC therapy.

Physalis angulata Linn. as a medicinal plant (Review)

“…By altering mitochondrial function, physalin B causes G2/M cell cycle arrest and cell death in human non-small cell lung cancer cells (A549) and a cell line for human breast cancer (MCF-7) affects p53-dependent signaling. The survival and proliferation of the undifferentiated gastric cancer cell line, HGC-27, and the ability to produce clones were all inhibited by physalin B, which induces G0/G1 cell cycle arrest and caspase 8, 3, 7 and poly (ADP-ribose) polymerase cleavage ( 17 ). In 2006, Magalhães et al ( 18 ) conducted in vivo studies investigating the antitumor activity of P. angulata L. using mice bearing sarcoma 180 tumor cells, confirming the antitumor activity of physalin B and D.…”

“…P. angulata L. contains active ingredients that have medicinal properties. These active substances are: i) Physalin A in the roots, with antiparasitic properties ( 23 ), ii) physalin B in the whole plant, with anti-inflammatory, antiparasitic, antibacterial, anticancer and antifibrotic properties ( 10 , 16 , 17 , 27 , 29 , 31 , 37 , 43 ), iii) physalin D, F, G in the whole plant, with anti-inflammatory, antiparasitic and antibacterial properties ( 11 , 20 , 23 , 32 , 34 , 43 ), iv) physalin E in the whole plant, with anti-inflammatory and antiparasitic properties ( 23 ), v) physalin H in the root, with antiparasitic properties ( 20 , 31 ), vi) withangulatin A in the fruit, with antidiabetic properties ( 35 ) and vii) physangulatin A in the leaves and stems, with anti-inflammatory properties ( 35 ). The active substances in P. angulata L. are also presented in Table II and Fig.…”

Therapeutic Applications of Physalins: Powerful Natural Weapons

“…In general, the cytotoxic activity of physalins was shown to be related to induction of programmed cell death ( Vandenberghe et al, 2008 ; Hsu et al, 2012 ; Wu et al, 2012 ; He et al, 2013a ; Ma et al, 2015 ; Fang et al, 2021 ; Yang et al, 2021 ). Physalins A, B, and F may trigger apoptosis through activation of the intrinsic pathway of poly (ADP-ribose) polymerase (PARP) cleavage ( Wu et al, 2012 ; He et al, 2013a ; Ma et al, 2015 ).…”

“…In this sense, Yang et al (2021) also concluded that physalin F was able to induce apoptosis in HT1080 cells mainly through the inhibition of the enzyme isocitrate dehydrogenase (IDH). Conversely, Fang et al (2021) demonstrated that, when physalin B treatment was performed in HGC-27 cells, the cell cycle-related proteins cyclin D1, cyclin D3, CDK4, CDK6, cyclin E, and the phosphorylated retinoblastoma tumor suppressor protein (p-Rb) were downregulated in a concentration-dependent manner, without activation of the intrinsic apoptosis pathway. Another important finding is that physalins stimulate the production of reactive oxygen species (ROS) and NO, which are important mediators responsible for triggering cell death by apoptosis ( Wu et al, 2012 ; He et al, 2013b ; He et al, 2014 ).…”

Development of o-aminobenzamide salt derivatives for improving water solubility and anti-undifferentiated gastric cancer

“…And its mortality rate ranks third among malignant tumors ( Ajani et al, 2022 ). Its 5-year survival rate is around 20%, posing a serious threat to human health ( Fang et al, 2021 ; Guo et al, 2021 ). In 2018, the number of newly diagnosed cases of stomach cancer is well over one million, and the number of deaths is increasing every year ( Zhao et al, 2016 ; Zhang and Yu, 2020 ).…”