Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities.

Area of Science:

• Natural Products Chemistry
• Pharmacology
• Cancer Biology

Background:

• Panax stipuleanatus rhizomes are a source of bioactive compounds.
• Oleanane-type triterpenoids are known for their diverse pharmacological activities.
• Identifying novel cytotoxic agents is crucial for cancer therapy.

Purpose of the Study:

• To isolate and identify oleanane-type triterpenoids from Panax stipuleanatus.
• To evaluate the cytotoxic activities of these compounds against cancer cell lines.
• To elucidate the mechanisms underlying their cytotoxic effects.

Main Methods:

• Methanol extraction of Panax stipuleanatus rhizomes.
• Isolation and structural elucidation of triterpenoids using spectroscopic data.
• In vitro cytotoxic activity assays against HL-60 (leukemia) and HCT-116 (colon cancer) cell lines.
• Apoptosis pathway analysis, including assessment of apoptotic bodies, caspase activation, and protein expression (DR-5, Bax, Bcl-2, PARP).
• Analysis of ERK1/2 MAPK pathway activation.

Main Results:

• One new and ten known oleanane-type triterpenoids were isolated.
• Compound 1 (spinasaponin A methyl ester) showed significant cytotoxicity against HL-60 (IC50=4.44 μM) and HCT-116 (IC50=0.63 μM).
• Compound 2 (pseudoginsenoside RP(1) methyl ester) exhibited potent cytotoxicity against HCT-116 (IC50=6.50 μM).
• Compounds 1 and 2 induced apoptosis in HL-60 and HCT-116 cells, evidenced by increased apoptotic bodies.
• Both compounds activated intrinsic and extrinsic apoptosis pathways and ERK1/2 MAPK in HCT-116 cells.
• Structure-activity relationship suggests a carboxyl group at position-28 is crucial for cytotoxic effects.

Conclusions:

• Compounds 1 and 2 are potent cytotoxic agents with potential as anti-cancer drugs.
• Apoptosis induction via intrinsic and extrinsic pathways, possibly mediated by ERK1/2 MAPK activation, is the primary mechanism of action.
• The carboxyl group at position-28 of the oleanane skeleton is important for cytotoxic activity.