Anticancer effect of SZC017, a novel derivative of oleanolic acid, on human gastric cancer cells

Abstract

Abstract. Oleanolic acid (OA) and its several derivatives possess chemopreventive and chemotherapeutic functions against a series of cancer types. Many chemotherapeutic compounds are effective in improving the quality of life and prolonging the survival of patients with gastric cancer, therefore progress in the treatment of gastric cancer, especially the anticancer effects of OA derivatives must be achieved. The inhibitory effect of SZC017, a newly synthesized derivative of OA, on cell viability was determined by MTT assay. Furthermore, flow cytometry, transmission electron microscopy, and western blot analysis revealed that the inhibition of cell viability by OA was mediated by triggering the intrinsic apoptosis of gastric cancer cells, and inducing S phase arrest of SGC7901 cells. Mechanistically, SZC017 was effective against gastric cancer cells via inhibiting Akt/NF-κB signaling and topoisomerase I and IIα proteins. Taken together, our data indicate that SZC017 may be a potential chemotherapeutic agent against gastric cancer cells.

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

“…The anticancer effects of oleanolic acid have been evaluated in many cancer types, including liver cancer [49,50,51,52], lung cancer [53,54], breast cancer [55], colon cancer [56,57,58], bladder cancer [59], prostate cancer [60], pancreatic cancer [61,62], gastric cancer [63], gallbladder cancer [64], osteosarcoma [65], hematological malignancies, e.g., leukemia [66], as well as in central nervous system cancers, such as malignant glioma [67,68]. …”

“…In addition, the isomer of oleanolic acid, ursolic acid, inhibited TGF-β/Smad signaling pathways with the antagonistic activity in the low micromolar range ( IC 50 = 6.9 µM) [78]. Moreover, oleanolic acid also inhibited topoisomerase I and IIα proteins, which are key enzymes involved in tumor cell proliferation, by relaxing DNA supercoiling inside cells [63]. It has been demonstrated that topoisomerase inhibition activates the NF‑κB pathway [79].…”

“…It has been demonstrated that topoisomerase inhibition activates the NF‑κB pathway [79]. The suppression of Top-I and Top-IIα resulted in the inhibition of the NF‑κB pathway via p‑IκBα and p‑p65‑dependent manner [63]. …”

“…Oleanolic acid induced apoptosis of tumor cells in numerous cancer cell lines, including acute myeloid leukemia [85], liver cancer cells [50,51], osteosarcoma cells [65], non-small cell lung cancer cells (NSCLC) [53], breast cancer cells [55,86], gastric cancer cells [62,87], pancreatic cancer cells [63], prostate cancer cells [61], bladder cancer cells [59], and colorectal cancer cells [58]. …”

Induction of autophagy by an oleanolic acid derivative, SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells

“…SZC017 were synthesized and authenticated by us (Gao et al, ). Dulbecco's modified Eagle medium (DMEM), trypsin‐EDTA, and Fetal bovine serum (FBS) were purchased from Gibco (Grand Island, NY, USA).…”