Secreted protein acidic and rich in cysteine antagonizes bufalin-induced apoptosis in gastric cancer cells

Abstract

Bufalin is an active compound in the traditional Chinese medicine Chan Su, which has been shown to induce apoptosis in a range of cancer cell types. However, certain gastric cancer cells are known to be resistant to bufalin. Intracellular secreted protein acidic and rich in cysteine (SPARC) regulates proliferation and apoptosis. This study aimed to evaluate the role of SPARC in bufalin-induced apoptosis in SGC7901 and MGC803 gastric cancer cells. SGC7901 cells with high SPARC expression were more resistant to bufalin than MGC803 cells with low SPARC expression. This resistance was significantly reversed by small interfering (si)RNA-mediated knockdown of SPARC. Furthermore, it was shown that SPARC negatively regulated bufalin-induced intrinsic apoptosis by protecting mitochondrial integrity, decreasing the release of cytoplasmic cytochrome c and increasing the ratio of Bcl-2/Bax. In addition, SPARC overcame bufalin-induced G2/M phase arrest by increasing levels of Cyclin B1 and Cyclin A protein expression. SPARC also activated cellular survival signals, including Src and Akt, but not extracellular signal-regulated kinase. This study demonstrated that SPARC antagonizes bufalin-induced apoptosis via inhibition of the intrinsic apoptosis pathway, inhibition of cell cycle arrest and activation of certain pathways involved in proliferation. This provides novel evidence for SPARC as a potential target by which to sensitize gastric cancer cells to bufalin.

SPARC expression in gastric cancer predicts poor prognosis: Results from a clinical cohort, pooled analysis and GSEA assay

“…Our previous data showed a high expression level of SPARC in SGC7901 GC cell line [20]. SPARC was decreased in SGC7901/Adr cell line, comparing with the parental cell line SGC7901 (Supplementary Figure S4).…”

“…We and some other scientists have demonstrated that SPARC in cancer cells could regulate the apoptosis, prohibit the angiogenesis and promote the invasion and the proliferation of tumors [18–20, 25]. In cancer stroma, SPARC regulates extracellular matrix (ECM) assembly, exhibits anti-adhesive function, and promotes emigration and invasion [3].…”

“…Adriamycin sensitivity of SGC7901 with or without SPARC siRNA transfection was further investigated using MTT assay. The detailed information and the techniques for cell culture, Western Blot, siRNA, and MTT assay were described in our previous study elsewhere [20, 47] and the current Supplementary File S1.…”

Bufalin Inhibits hTERT Expression and Colorectal Cancer Cell Growth by Targeting CPSF4

“…Previous studies have shown that bufalin inhibits the proliferation of leukemia [6], prostate cancer [5], gastric cancer [25], and osteosarcoma [26]. Therefore, we investigated whether bufalin could also inhibit cell proliferation in SW620 cells.…”

Radiosynthesis and pharmacokinetics of [¹⁸F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

“…Bufalin has multi-target antitumor effect in a range of tumors, such as hepatocellular carcinomas,2 colorectal cancer,3 leukemia,4 gastric cancer,5 and osteosarcoma 6. Preceding findings have revealed that the anticancer activity of bufalin could be attributed to its prevention of cell proliferation, instruction of apoptosis, disturbance of the cell cycle, and modulation of the immune response 7–9.…”