Gambogic acid improves non‐small cell lung cancer progression by inhibition of mTOR signaling pathway

Abstract

Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy. Western blot analysis showed that GA treatment suppressed the activation of Akt, mTOR, and S6. In addition, using a GA and rapamycin combination induced more cell death compared to either GA or rapamycin alone. In summary, GA may have utility as an adjunct therapy for non-small cell lung cancer (NSCLC) patients through autophagy-dependent cell death, even when cancer cells have developed resistance to apoptosis.

Retracted Article: The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction

“…It is reported that GA inhibited the growth of different types of cancer, including lung cancer, colorectal cancer, prostate cancer and breast cancer, hepatocellular carcinoma, multiple myeloma and leukemia. [14][15][16][17][18][19][20] The antitumor mechanism of GA may be related to inducing apoptosis, inhibiting telomerase, blocking NF-kB signaling pathway and enhancing the accumulation of reactive oxygen species. 21 However, the potential role and molecular mechanisms of GA in cervical cancer remain poorly understood.…”

Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathway

“…Recent studies have shown that dysfunction in PTEN/PIK3/AKT/mTOR signaling is involved in tumorigenesis 36 . As an important tumor suppressor gene, PTEN negatively regulates PI3K/AKT/mTOR pathway, inhibiting cell growth and proliferation 37 , 38 . The findings in this study suggest that GA attenuates ESCC cell growth presumably through regulating PTEN and PI3K/AKT/mTOR pathway.…”

Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer

“…Gambogic Acid (GA) is a xanthonoid compound derived from Garcinia hanburyi with anti-cancer activity proved in vitro and in vivo [108].…”

“…The effect on cell death could be markedly reduced by the addition of autophagy inhibitors -3-MA and CQ. Moreover, treatment with GA was linked to Akt/mTOR pathway inhibition and the addition of mTOR inhibitor -rapamycin further increased autophagic flux and cell death [108].…”