AI Article Synopsis
- Cancer is a significant health challenge, with natural plant-based compounds showing promise in developing anti-cancer treatments, particularly in regions rich in therapeutic plants like the Darjeeling Himalayas.
- The study focused on isolating a specific phytosteroid (A11) from A. rivularis and found that it inhibits the activity of human dihydrofolate reductase (hDHFR), a key enzyme in cancer cell growth, with promising binding metrics and cytotoxic effects on kidney and liver cancer cells.
- A11's efficacy in inducing apoptosis (programmed cell death) in cancer cells was demonstrated through changes in cell morphology and increased reactive oxygen species (ROS), indicating its potential as a novel therapeutic agent for cancer treatment
Article Abstract
Background: Cancer remains a major world health issue due to its high morbidity and mortality rate. Plant based natural products (NPs) have played vital role in discovery of valuable anti-cancer drugs. Darjeeling Himalayan region has a rich diversity of therapeutic plants that can be utilized for development of novel drugs.
Aim: We previously reported cytotoxic potential of rhizome extract of A.rivularis, a Darjeeling himalayan herb. Present study reports isolation and characterization of a phytosteroid from the plant rhizome in a bioassay-guided approach and evaluation of its anti-tumorigenic potential.
Results: The phytosteroid was characterized as stigmasta-5(6), 22(23)-dien-3-beta-yl acetate (A11) by various spectrometric techniques (IR, NMR, MS etc.). The catalytic inhibition and structural alteration of human dihydrofolate reductase (hDHFR) by A11 was evaluated using methotrexate (MTX), a DHFR inhibitor anticancer drug as a reference. A11 inhibited hDHFR activity with IC values of 1.20 μM A11 caused concentration dependent quenching of tryptophan fluorescence of hDHFR suggesting its effect on alteration of enzyme structure. Molecular docking of A11 on crystal structure of hDHFR revealed significant interaction with free energy of binding and Ki values of -10.86 kcal/mol and 11 nM, respectively. Subsequent in vitro studies at cellular level showed a relatively greater cytotoxic effect of A11 against human kidney (ACHN, IC 60 μM) and liver (HepG2, IC70 μM) cancer cells than their respective normal cells (HEK-293, IC 350 μM and WRL-68, IC 520 μM). Scanning electron microscopy of A11 treated cells revealed the morphological feature of apoptosis, like cell rounding and surface detachment, membrane blebbing, loss of cilia and increased number of pores of decreased sizes. A11 mediated apoptosis of cancer cells was found to be correlated with induction of intracellular of reactive oxygen species (ROS) level and fragmentation of genomic DNA.
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| http://dx.doi.org/10.1016/j.cbi.2022.109935 | DOI Listing |
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