RETRACTED ARTICLE: Lupeol inhibits proliferation and induces apoptosis of human pancreatic cancer PCNA-1 cells through AKT/ERK pathways

Abstract

Lupeol, a dietary triterpene, present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including anti-cancer activities both in vitro and in vivo. However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anti-cancer activity and the underlying mechanisms of lupeol on human pancreatic cancer proliferating cell nuclear antigen 1 (PCNA-1) cells in vitro and in vivo. Lupeol significantly inhibited the proliferation of the cells in dose- and time-dependent manners and induced apoptosis as well as cell cycle arrest in G0/G1 phase by upregulating P21 and P27 and downregulating cyclin D1. The expression of apoptosis-related proteins in cells was evaluated by western blot analysis, and we found that lupeol induced cell apoptosis by decreasing the levels of p-AKT and p-ERK. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of lupeol in PCNA-1 cells, demonstrating the important role of AKT in this process. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of p-AKT and p-ERK in tumor tissues following lupeol treatment, consistent with the in vitro results. Therefore, these findings indicate that lupeol can inhibit cell proliferation and induce apoptosis as well as cell cycle arrest of PCNA-1 cells and might offer a therapeutic potential advantage for human pancreatic cancer chemoprevention or chemotherapy.

Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines

“…In 2011, Shaari et al reported identification of phytochemical compounds from the methanol extract of MP, which include lupeol, oleanolic acid, kokusaginine and genistein [35]. These compounds have been reported to exhibit anticancer activity [36–38]. In the present study, although MP-MeOH was observed to show the highest TPC and TFC values, the antioxidant activity was not correlated to polyphenols content.…”

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells in�vitro

“…For example, the ERK1/2 pathway is the classic cell growth signaling of the mitogen-activated protein kinase (MAPK) pathway. Activated ERK1/2 will promote cell survival and proliferation by phosphorylating many nuclear transcription factors (23). The present study showed that lenalidomide alone or in combination with cisplatin could reduce p-ERK levels in TNBC cells, although cisplatin alone induced p-ERK level.…”

RETRACTED: Lupeol Induces Apoptosis and Cell Cycle Arrest of Human Osteosarcoma Cells Through PI3K/AKT/mTOR Pathway

“…For instance, Saleem et al 17 found that lupeol could inhibit proliferation of human prostate cancer cells by targeting b-catenin signaling. We have also shown that lupeol could inhibit proliferation and induce apoptosis of human pancreatic cancer proliferating cell nuclear antigen 1 cells through AKT/extracellular signal-regulated kinase (ERK) pathways, 21 and lupeol could induce apoptosis and inhibit invasion in gallbladder carcinoma GBC-SD cells by suppression of epidermal growth factor receptor/matrix metallopeptidase 9 signaling pathway. 22 However, little is known about its effects on human osteosarcoma, and the precise mechanism involved remains largely unknown.…”