Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

Abstract

Abstract. Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagyrelated genes affected by MRGX. Administration of MRGX at 100 µg/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 µg/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 µg/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.

Ginsenoside metabolite compound K induces apoptosis and autophagy in non-small cell lung cancer cells via AMPK–mTOR and JNK pathways

“…In contrast, plenty of studies suggested that inhibition of autophagy promoted the development of lung and liver cancers (Qu et al 2003;Yue et al 2003). Recent research found that modified regular ginseng extract (containing Rh2, Rg3, C-K and protopanaxatriol type) could induce autophagy in lung cancer cells (Yoo et al 2017).…”

UNBS5162 inhibits the proliferation of human A549 non‐small‐cell lung cancer cells by promoting apoptosis

“…Chemotherapy and γ‐irradiation can inhibit cancer cell proliferation, but can also kill normal cells and cause many side effects, such as loss of immunity. Studies have shown that the five‐year survival rate in patients with lung cancer is less than 15% as a result of chemotherapy resistance; 4,5 therefore, many researchers have attempted to develop novel anticancer agents …”

“…Studies have shown that the five-year survival rate in patients with lung cancer is less than 15% as a result of chemotherapy resistance; 4,5 therefore, many researchers have attempted to develop novel anticancer agents. [6][7][8] Naphthalimides are DNA intercalating agents that have shown high preclinical anticancer activity against a variety of human tumor cells. 9 Amonafide, the first naphthalimide evaluated in clinical trials as a potential anticancer agent failed to enter phase III trials because of dose-limiting bone marrow toxicity.…”

Awareness and Use of Complementary and Alternative Medicine in Korean Lung Cancer Patients

“…This definition implies that these interventions are not fully proven to be effective or safe, nor are they based on scientific evidence. Some experimental, retrospective studies or small prospective studies have shown the potential efficacy or safety of CAM, such as oncothermia 25,26 , high-dose vitamin C 25,27 , mistletoe 11,28,29 , thymosin alpha 1 30,31 , or oriental medicine 10,12,[32][33][34] . However, some studies have shown the harmful effects of CAM, such as treatment delay, treatment refusal, and increased mortality 7,13,35 .…”