Abstract
Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3β, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.
Highlights
Lung cancer is presently one of the most harmful human diseases with the highest morbidity throughout the world, which has an incidence of 20.9 million new cases and 18.0 million deaths in 2018 [1]
It has been reported that the n-butanol extract of C. lanceolata root induced the apoptosis of human colon cancer HT-29 cells via ROS accumulation and polyamine depletion [15]
Six compounds were isolated from C. lanceolata, and their structures were characterized as syringin (1), codonopilodiynoside A (2), lobetyol (3), (+)-isolariciresinol (4), lobetyolin (5), and atractylenolide III (6) by comparing their physical and spectral data (HR-MS, HPLC, 1H-NMR, and 13C-NMR) with previous reports [20–22, 31, 32]
Summary
Lung cancer is presently one of the most harmful human diseases with the highest morbidity throughout the world, which has an incidence of 20.9 million new cases and 18.0 million deaths in 2018 [1]. The roots of C. lanceolata are used as a folk medicine for treating various lung diseases, including cough, bronchitis, edema, asthma, and lung cancer over thousands of years [9–12]. It contains a wide variety of distinctive metabolites (e.g., polysaccharides, saponins, and polyacetylenes) [9, 13, 14]. It has been reported that the n-butanol extract of C. lanceolata root induced the apoptosis of human colon cancer HT-29 cells via ROS accumulation and polyamine depletion [15]. Its methanol extract induced the apoptosis of human oral cancer HSC-2 cells through activation of the Bak pathway [16]. The polyacetylenes of C. lanceolata (CLP) loaded onto the chromatographic column to the bioactive polyacetylenes of C. lanceolata (CLP) were yielded through silica gel chromatography separation, and their antitumor potentials were assessed in A549 cells and in tumorbearing mice
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