Plant-Derived Protease Inhibitors LC-pi (Lavatera cashmeriana) Inhibit Human Lung Cancer Cell Proliferation In Vitro

Abstract

The objective of this study was to check the anticancer activity of purified protease inhibitors of Lavatera cashmeriana viz LC-pi I, II, III, and IV (Lavatera cashmeriana protease inhibitors) on A549 (lung) cell. It was found that LC-pi I and II significantly inhibited the proliferation of A549 cells with IC₅₀ value of 54 μg/ml and 38 μg/ml, respectively, whereas inhibition by LC-pi III and IV was negligible. LC-pi I and II were further found to inhibit formation of colonies in a dose-dependent manner. Also, both inhibitors were found to induce apoptosis causing chromatin condensation and DNA fragmentation, without loss of mitochondrial membrane potential. Cell cycle revealed a significant increase of subG₀/G₁ phase cells that are apoptotic cells. We also demonstrated a dose-dependent decrease in migration of A549 cells on cell migration assay by both inhibitors. Taken together, we demonstrate that LC-pi I and II inhibited proliferation through arresting cells before apoptosis, inducing apoptosis and inhibiting cell migration in human lung cancer cells, but the study warrants further investigation. Our results support the notion that plant protease inhibitors may have the potential to advance as chemopreventive agents.

Mechanistic study on the anti‐proinflammatory activity of Kunitz type inhibitor fromCaesalpinia decapetalaseeds

“…CdTI cytotoxicity on A549 and RAW264.7 cells was compared with that of other serine legume PIs previously described. Earlier, Lavatera cashmeriana PI shown cytotoxicity against a human lung cancer cell line (NCIH322), with an IC50 value of 36.2 µg/mL, which was greater than the values found in our investigation 41 . Cicer arietinum (chickpea) PIs (25−400 µg/mL) significantly reduced the viability of MDA‐MB‐231 breast cancer cells, as well as PC‐3 and LNCaP prostate cancer cells 9 …”

“…Earlier, Lavatera cashmeriana PI shown cytotoxicity against a human lung cancer cell line (NCIH322), with an IC50 value of 36.2 µg/mL, which was greater than the values found in our investigation. 41 Cicer arietinum (chickpea) PIs (25−400 µg/mL) significantly reduced the viability of MDA-MB-231 breast cancer cells, as well as PC-3 and LNCaP prostate cancer cells. 9 Neutrophil serine proteases cause noninfectious inflammatory responses.…”

Enzymatic Pea Protein Hydrolysates Are Active Trypsin and Chymotrypsin Inhibitors

“…The physiological roles of protease inhibitors are diverse and include regulation of various cellular activities, prevention of organ structure deterioration (e.g., the pancreas), and inhibition of viral infections [12]. This is because proteases are involved in the irreversible hydrolysis of peptide bonds; therefore, unregulated proteolysis can lead to serious metabolic disorders that precipitate the onset and progression of diseases such as cancer, cardiovascular disorders, neurodegeneration, and chronic inflammation [12,13,14,15,16,17]. As a preventive tool, protease inhibitors have been shown to inhibit proliferation of preadipocytes, which suggests an anti-obesity potential [18].…”