Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest and Apoptosis-Inducing Activity in RKO Colon Cancer Cells

Abstract

Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10-15) were separated from an extract of the branches and leaves of Jatropha gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8, 9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons that have been found only in compounds isolated from plants of the Jatropha genus. The absolute configurations of 1-10 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer cells with an IC value of 2.6 μM. Morphological features of apoptosis and antimigration activities were evaluated in 12-treated RKO cells. Compound 12 effectively induced apoptosis of RKO, which was associated with G/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 12 significantly induced RKO cell apoptosis in a dose-dependent manner.

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

“…In addition, SAR1B mRNA expression was 7.23-fold higher than the level of GADPH in RKO cells, which was consistent with HCT116 and SW620 cells. The present study selected RKO cells for the validation of functional importance of SAR1B in CRC, which has been widely used in previous CRC studies ( 23 – 26 ).…”

Euphohyrisnoids A and B, Two Highly Rearranged Lathyrane Diterpenoids from Euphorbia lathyris

“…The NOE interaction of H-4/H 2 -7 indicated that C-7–C-8 bond was α-orientationally bridged between C-6 and C-9. Configuration of Δ double bond was assigned as Z by NOE cross-peak of H-11/H 3 -20. Finally, the structure of 1 was secured by a single-crystal X-ray diffraction, which also allowed the determination of its absolute configuration as 2 S ,3 S ,4 S ,6 R ,9 S ,13 R ,15 R with the Flack parameter = 0.02(6) (see Figure , given later in this work).…”

“…Based on the coisolated major component euphorbia factor L 3 ( 3 ), a putative biosynthetic pathway for euphohyrisnoids A ( 1 ) and B ( 2 ) was proposed in Scheme . Briefly, 3 underwent acid-mediated cyclopropane-opening (C-10–C-11 cleavage), followed by elimination of H-9 to afford an intermediate i with a 10,11- seco -lathyrane skeleton . The keto–enol tautomer of i ( ii ) further underwent an intramolecular Diels–Alder reaction between the terminal double bond C-6C-17 and the diene system C-12C-11–C-9C-10 to give intermediate iiia , constructing the tricyclo­[7.2.2.0 1,7 ] ring system.…”

Daphnane Diterpenoids from Daphne genkwa Inhibit PI3K/Akt/mTOR Signaling and Induce Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells

“…The most representative components of D. genkwa are the daphnane-type diterpenes, which show various biological activities, including antineoplastic, antileukemic, antifertility, , and skin-irritant activities . As part of our screening program to explore antineoplastic compounds from natural sources, the petroleum ether extract of D. genkwa showed cytotoxic inhibitory activity. Subsequent chemical investigation of this extract led to the isolation of seven new compounds ( 1 – 7 ) and 15 known analogues ( 8 – 22 ).…”