Therapeutic potential of IBP as an autophagy inducer for treating lung cancer via blocking PAK1/Akt/mTOR signaling

Abstract

Lung cancer is the most frequent and fatal malignancy in humans worldwide, yet novel successful drugs for control of this disease are still lacking. Ipomoea batatas polysaccharides (IBPs) have been implicated in inhibiting diverse cancer types, but their functions in mitigating lung cancer are largely unknown. In this study, we identify a role of IBP in inhibiting lung cancer proliferation. We found that IBP significantly impedes the proliferation of lung cancer cells by inducing cytostatic macroautophagy both in vitro and in vivo . Mechanistically, IBP specifically promotes ubiquitination-mediated degradation of PAK1 (p21-activated kinase 1) and blocks its downstream Akt1/mTOR signaling pathway, leading to increased autophagic flux. In lung cancer xenografts in mice, IBP-induced cytostatic autophagy suppresses tumor development. Through site-directed mutational analysis, the underlying signaling augments ubiquitination via PAK1-ubiquitin interaction. Collectively, this work unravels the molecular mechanism underpinning IBP-induced cytostatic autophagy in lung cancer and characterizes IBP as a potential therapeutic agent for lung cancer treatment.

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“…Primers for quantitative real-time PCR are shown in Table 1 . The qRT-PCR assay was manipulated using iTag Universal SYBR Green Supermix (Bio-Rad, Hercules, CA, USA) in a CFX Connect Real-Time PCR Detection System (Bio-Rad), and the results were calculated through the 2 2DDCt threshold methodology following normalization with GAPDH [ 61 ].…”

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

“…Thus, the subcutaneous xenogeneic model of Professor Mu and colleagues 22 was adopted. This model was also used by Professor Bu and colleagues 23 in their study of lung cancer treatment, implying that the conclusion obtained using this model was credible. According to the results of the present experiments, the subcutaneous xenogeneic model was relatively stable ( Figure S1 ).…”

“…Cell viability was determined by EdU (RiboBio, Guangzhou, China) assay. 23 The cells were plated at 1 × 10 4 cells per well in 96-well microtiter plates with 100 μL complete culture medium and treated with designated PSPD3R concentrations (0, 25, 50, and 75 μM) for 24 h at 37°C in a humidified chamber. Treatment with each PSPD3R concentration was replicated in three wells.…”

“…Immunohistochemical analysis was performed as previously described. 23 Tumor tissues from three independent mice were fixed in 4% paraformaldehyde for 2 h and embedded in paraffin following a routine histologic procedure. Tissue blocks were then cut into 4 μm slices, dewaxed, rehydrated, autoclaved for antigen retrieval, blocked with 3% bovine serum albumin (BSA; Beyotime) for 3 h, and finally incubated with rabbit polyclonal antibodies (Abs) against Ki67 (Proteintech, Wuhan, China) and Alexa Fluor 488-conjugated goat anti-rabbit secondary Ab (Proteintech).…”

Plant polysaccharides with anti-lung injury effects as a potential therapeutic strategy for COVID-19

“…Related research suggests that Ipomoea batatas (L.) Lam. [Convolvulaceae; Ipomoea radix] polysaccharide (IBP) could promote autophagosome formation via activating the expression of Beclin1 and Atg5 ( Bu et al, 2020 ). Moreover, treatment with IBP in lung cancer cells may enhance autophagy by decreasing the interaction of Beclin1/Bcl-2.…”