A herbal formulation inhibits growth and survival of lung cancer cells through DNA damage and apoptosis - in vitro and in vivo studies

Lung cancer is among the most common and lethal types of cancer in the world. The Unani system of medicine is an ancient traditional medicine that utilizes various medicinal plants. This study aimed to investigate a herbal formulation, Safoof Lajward (SL) which has not been studied for its chemopreventive and anticancer properties to date. Methanolic extract of SL was chemically characterised by GC-MS and HPLC and its in vivo toxicity was evaluated on C57BL/6 mice. Anticancer effects of SL were studied on human lung carcinoma cells using trypan blue stain, clonogenicity, cell cycle distribution, apoptosis, mitochondrial membrane potential (ΔΨm), and immunoblotting assays. The antitumor effect of SL was evaluated on A549 lung tumor xenograft in nude mice. SL showed various bioactive phytochemicals like resveratrol, epicatechin, ellagic acid, epicatechin gallate, quercetin, and vanillin. The orally administered SL (50 and 100 mg/kg) elevated the hepatic xenobiotic-metabolizing enzymes (phases I & II). SL inhibited the growth and survival of lung cancer cells by accumulating cells at the sub-G1 phase and increasing apoptotic cells by 47-fold and caused dissipation of ΔΨm by 7-fold with increased expression of Bax and decreased expression of Bcl-2 proteins. SL induced DNA damage by reducing Chk1, Chk2, and Rad51 proteins. SL strongly suppressed A549 lung tumor xenograft growth by 45 % and tumor weight by 53 % without any toxicity in mice. SL inhibited Ki-67 and PCNA expression and enhanced Bax/Bcl-2 ratio, cleaved PARP, and cleaved caspase 3, but decreased Chk1, Chk2, and Rad51 proteins in tumors. Together, these findings suggested that SL has chemopreventive efficacy as well as strong anti-proliferative and pro-apoptotic activities against lung cancer.