Rottlerin promotes autophagy and apoptosis in gastric cancer cell lines

Abstract

It is widely accepted that apoptosis is closely associated with cancer cell death. However, whether autophagy induces tumor cell death has not been fully elucidated. Various studies have discussed the antitumor properties of rottlerin in human malignancies. The current study aimed to investigate the effects of rottlerin, a natural product isolated from the kamala tree (Mallotus philipensis), on growth inhibition and autophagy in gastric cancer (GC) cell lines in vitro. The results of the present study demonstrated that rottlerin suppressed cell growth, induced autophagy and apoptosis, and reduced migration and invasion in the SGC-7901 and MGC-803 GC cell lines. Furthermore, rottlerin led to microtubule-associated protein 1 light chain 3β-II augmentation and the enrichment of autophagosomes. In addition, the protein expression levels of mechanistic target of rapamycin kinase and S-phase kinase-associated protein 2 were downregulated in GC cells following rottlerin treatment, which is associated with autophagy. The protein levels of caspase-3, cleaved-caspase-3, total poly (ADP-ribose) polymerase (PARP) and cleaved-PARP exhibited no marked alterations in the GC cells following rottlerin treatment, indicating that caspases were likely not involved in rottlerin-induced GC apoptosis. In summary, the results of the present study indicate that rottlerin may inhibit invasion and promote apoptosis in GC cells, which may be mediated by the activation of autophagy. Therefore, rottlerin may be of value in the treatment of GC.

Effect and mechanism of action of SLP‑2 on the apoptosis and autophagy of gastric cancer cells

“…The inhibition of apoptosis and the induction of autophagy have been documented in several types of tumor, including gastric cancer ( 15 ). In recent years, the development of autophagy inhibitors, as well as inducers of tumor cell apoptosis to a certain extent, has attracted increasing attention ( 16 , 22 – 24 ).…”

Emerging Potential of Naturally Occurring Molecules against Gastric Cancer: Insights Molecular Mechanism and Therapeutic Targets

“…Two single compounds and two plant extracts were reported to induce autophagy along with apoptosis against gastric cancer cells (Table 7). Rottlerin, extracted from Mallotus philipensis Muell (Euphorbiaceae), induced autophagy and caspase independent apoptosis against SGC-7901 and MGC-803 cells [105]. Autophagy is induced by downregulating mTOR and S-phase kinase-associated protein…”

“…The studies performed cell cycle analysis through flow cytometry to observe cell cycle distribution, albeit the proteins responsible for the event were not confirmed in a large portion of the investigations. Berberine, TTF, ginsenoside-Rh2, crosolic acid, rottlerin, grifolin, methanol extract of aster incises (Asteraceae), organic extract of Amorphophallus konjac K.Koch Tuber (Araceae), and xiao tan he wei decoction induced G0/G1 phase cell cycle arrest [38,45,49,58,62,87,90,105,109]. Toosendanin increased the proportion of cells in the G1 and S phase [67,68].…”

Ratlarda Rottlerin’in Otofaji Üzerine Etkili Doz Düzeyinin Araştırılması

“…Rottlerin, çeşitli hücre kültürleri üzerinde yapılan çalışmalarda bir otofaji aktivatörü olarak kullanılmıştır [12][13][14] . Chhiber ve ark.…”