Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC50 value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC50 = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.

Metabolic Profiling, in vitro Cytotoxicity and in silico Investigation of Lycium shawii Roem. Extract

“…The scratch closures at IC 50 doses were smaller, measuring up to 17.2% at 24 hours and 35.8% at 48 h, reflecting the potential of the extract in reducing cell migration. Several in vitro studies have provided evidence that phytochemical compounds derived from L. shawii can impede the invasion and migration of various cell lines (Choi et al, 2013;Xiao and Guo, 2009;Shams et al, 2023).…”

Preliminary Structural Characterization of Selenium Nanoparticle Composites Modified by Astragalus Polysaccharide and the Cytotoxicity Mechanism on Liver Cancer Cells

“…Based on the successful preparation of stable nano-composites, we proceeded to study the inhibitory effects on HepG2 cells in vitro via an MTT test, morphological alterations, Annexin V-FITC/PI double staining method, cell cycle determination, ROS, and Δ Ψm level detection and obtained significant experimental results. As reported, the apoptotic cells were usually accompanied by some characteristic morphological features such as cellular membrane changes, shrinkage, nuclear concentration, and fragmentation [ 37 , 38 ]. The results demonstrated that AASP−SeNPs could effectively exert cytotoxicity and induce apoptosis in HepG2 cells, dose-dependently.…”

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis

“…Costunolide isolated from the stem of Lycium shawii initiated apoptosis in oral squamous cell carcinoma (OSCC) cell line CAL 27. This compound upregulated Bak, amplified the levels of cleaved caspases 3 and 6, and anti-apoptotic factor BCL2L1 in this cell line ( Shams et al, 2023 ). In platinum-resistant human ovarian cancer cells (MPSC1 and SKOV3), costunolide has been shown to act stronger than cisplatin in decreasing cell viability.…”