Trilliumosides K and L, two novel steroidal saponins from rhizomes of Trillium govanianum , as potent anti-cancer agents targeting apoptosis in the A-549 cancer cell line.

Autor: Lone BA; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Tabassum M; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Bhushan A; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Rani D; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Dhiman U; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Ahmad A; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Mir HA; Department of Ophthalmology, Pathology, and Cell Biology, Columbia University, New York, NY, United States., Gupta PN; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Mondhe DM; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Gairola S; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Plant Science and Agrotechnology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India., Gupta P; CSIR-Human Resource Development Centre, Academy of Scientific and Innovative Research, Ghaziabad, India.; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Jazyk: angličtina
Zdroj: Frontiers in chemistry [Front Chem] 2023 Dec 22; Vol. 11, pp. 1306271. Date of Electronic Publication: 2023 Dec 22 (Print Publication: 2023).
DOI: 10.3389/fchem.2023.1306271
Abstrakt: Two novel steroidal saponins, trilliumosides K ( 1 ) and L ( 2 ), were isolated from the rhizomes of Trillium govanianum led by bioactivity-guided phytochemical investigation along with seven known compounds: govanoside D ( 3 ), protodioscin ( 4 ), borassoside E ( 5 ), 20-hydroxyecdysone ( 6 ), 5,20-hydroxyecdysone ( 7 ), govanic acid ( 8 ), and diosgenin ( 9 ). The structure of novel compounds 1-2 was established using analysis of spectroscopic data including 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-ESI-MS) data. All isolated compounds were evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Compound 1 showed significant cytotoxic activity against the A-549 (Lung) and SW-620 (Colon) cancer cell lines with IC50 values of 1.83 and 1.85 µM, respectively whereas the IC50 value of Compound 2 against the A-549 cell line was found to be 1.79 µM. Among the previously known compounds 3 , 5 , and 9 , the cytotoxic IC50 values were found to be in the range of 5-10 µM. Comprehensive anti-cancer investigation revealed that Compound 2 inhibited in vitro migration and colony-forming capability in the A-549 cell line. Additionally, the mechanistic analysis of Compound 2 on the A-549 cell line indicated distinctive alterations in nuclear morphology, increased reactive oxygen species (ROS) production, and decreased levels of mitochondrial membrane potential (MMP). By upregulating the pro-apoptotic protein BAX and downregulating the anti-apoptotic protein BCL-2, the aforementioned actions eventually cause apoptosis, a crucial hallmark in cancer research, which activates Caspase-3. To the best of our knowledge, this study reports the first mechanistic anti-cancer evaluation of the compounds isolated from the rhizomes of T. govanianum with remarkable cytotoxic activity in the desired micromolar range.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Lone, Tabassum, Bhushan, Rani, Dhiman, Ahmad, Mir, Gupta, Mondhe, Gairola and Gupta.)
Databáze: MEDLINE
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