Antitumor lignanamides from the aerial parts of Corydalis saxicola.
BACKGROUND
Cancer is one of the leading cause of unnatural death globally. There is still a great need for effective anticancer agents from plant sources. Corydalis saxicola Bunting is a medicinal plant that is traditionally used to treat various diseases in southwest China. Previous phytochemical investigations of C. saxicola have focused on isoquinoline alkaloids that have been isolated, which have activity against anti-hepatitis B virus and inhibit DNA topoisomerase I. However, the exploration of other classes of constituents and their bioactivities needs further study.


OBJECTIVE
The aim of this study was to investigate the antitumor activity of isolated lignanamides as well as their detailed cellular proliferation, suppression, and cytotoxic mechanisms.


METHODS
Herbs were extracted and constituents were purified by chromatographic separation, including silica gel, ODS, MCI, Sephadex LH-20 and Preparative HPLC. The compound structures were elucidated by the use of UV, IR, NMR and MS spectral data. The cytotoxicity effects of all compounds from the MGC-803, HepG2, T24, NCI-H460, Spca-2, and HL-7702 cell lines were studied by MTT assays. The induction of apoptosis by corydalisin C was investigated using acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry.


RESULTS
Three new lignanamides, together with five known analogues, were isolated from the aerial parts of C. saxicola. Corydalisin C possessed the most potent inhibitory effects, with an IC50value of 8.81 ± 2.05µM against MGC-803 cells. SAR analysis showed that the sterics and chirality of lignanamides play a crucial role in pharmacologically relevant events. The antitumor activity was possibly due to the induction of cell apoptosis. Western blot experiments demonstrated that corydalisin C may induce apoptosis through both intrinsic and extrinsic apoptosis pathways, accompanied by down-regulating the expression of Bcl-2 and FasL in a time-dependent manner.


CONCLUSIONS
This study provides evidence that a lignanamide from the ethyl acetate extract of whole plants of C. saxicola showing potential in cancer treatment.
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China.
Bin
B
Zhang
Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu, China.
Rizhen
R
Huang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China.
Jing
J
Hua
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China.
Hong
H
Liang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China.
Yingming
Y
Pan
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China.
Lumei
L
Dai
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: liangdonggxnu@163.com.
Dong
D
Liang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: whengshan@163.com.
Hengshan
H
Wang
D000577:Amides / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D031311:Corydalis / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D017705:Lignans / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D035261:Plant Components, Aerial / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
D000577:Amides; D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans
Antiproliferative activities; Corydalis saxicola; Corydalisin; Gastric cancer cells; Lignanamides