Grape Seed Proanthocyanidins play the roles of radioprotection on Normal Lung and radiosensitization on Lung Cancer via differential regulation of the MAPK Signaling Pathway

Abstract

Radiation-induced lung injury (RILI) is a common serious complication and dose-limiting factor caused by radiotherapy for lung cancer. This study was to investigate radioprotective effects of grape seed proanthocyanidins (GSP) on normal lung as well as radiosensitizing effects on lung cancer. In vitro , we demonstrated radioprotective effects of GSP on normal alveolar epithelial cells (MLE-12 and BEAS/2B) and radiosensitizing effects on lung cancer cells (LLC and A549). In vivo , we confirmed these two-way effects in tumor-bearing mice. The results showed that GSP inhibited tumor growth, and played a synergistic killing effect with radiotherapy on lung cancer. Meanwhile, GSP reduced radiation damage to normal lung tissues. The two-way effects related to the differential regulation of the MAPK signaling pathway by GSP on normal lung and lung cancer. Moreover, GSP regulated secretion of cytokines IL-6 and IFN-γ and expression of p53 and Ki67 on normal lung and lung cancer. Our findings suggest that GSP is expected to be an ideal radioprotective drug for lung cancer patients who are treated with radiotherapy.

Grape Seed Proanthocyanidins Exert a Radioprotective Effect on the Testes and Intestines Through Antioxidant Effects and Inhibition of MAPK Signal Pathways

“…For example, proanthocyanidins play a protective role in ultraviolet-induced keratinocyte damage ( 44 ), oxidative stress-induced renal tubular cell apoptosis ( 45 ), and ionizing radiation-induced liver damage ( 46 ) and lymphocyte damage ( 47 ). Our previous experiments also confirmed that proanthocyanidins have radioprotective effects on lung epithelial cells and AHH-1 cells ( 18 , 48 , 49 ). In this study, our results show that proanthocyanidins can reduce the damage to mouse testicular stromal cells TM3 and human small intestinal crypt epithelial cells HIEC caused by ionizing radiation, reduce cell apoptosis, promote cell proliferation, and reduce DNA double-strand breaks.…”

Insight into the Progress on Natural Dyes: Sources, Structural Features, Health Effects, Challenges, and Potential

“…M3G as an adjuvant ingredient or nutritional supplement can prevent liver cancer by inhibiting proliferation, migration, and invasion-related pathways and promoting the apoptosis of liver tumor cells [ 147 ]. In addition, grape seed proanthocyanidins showed a radioprotective effect on normal lung cells and were considered an ideal radioprotective drug for lung cancer patients treated with radiotherapy [ 148 ]. Curcumin is a promising candidate for prevention and treatment of several cancers.…”

Proanthocyanidins-loaded complex coacervates-based drug delivery attenuates oral squamous cell carcinoma cells metastatic potential through down-regulating the Akt signaling pathway

“…In addition to PI3K/Akt, MAPKs pathway consisting of Erk, JNK, and p38 subfamily also presents another important mechanism for oral carcinogenesis ( 26 ). A few evidences have reported that grape seed PA can exert contradictory effects on the activation of these MAPKs ( 36 – 38 ). However, in our study, none of three pathways was affected by CCDC-PA.…”