Psiadin and plectranthone selectively inhibit colorectal carcinoma cells proliferation via modulating cyclins signaling and apoptotic pathways

• Published in: PloS one Vol. 16; no. 6; p. e0252820
• Main Authors: Orabi, Khaled Y, Abaza, Mohamed S, Luqmani, Yunus A, Al-Attiyah, Rajaa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-06-2021; Public Library of Science (PLoS)
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biology and Life Sciences; Cancer; Care and treatment; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Complications and side effects; Humans; Medicine and Health Sciences; Membrane Potential, Mitochondrial - drug effects; NF-kappa B - metabolism; Patient outcomes; Physical Sciences; Reactive Oxygen Species - metabolism; Research and analysis methods; Signal Transduction - drug effects; Terpenes - pharmacology; Kuwait
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0252820

Three scarce terpenes, psiadin, plectranthone and saudinolide, were obtained after chromatographic isolation and purification from the aerial parts of the respective plants. Their identities were established based on their spectral data. Their anticancer effects against two human colorectal carcinoma cell lines, CCL233 and CCL235, along with the potential molecular mechanisms of action, were explored. Psiadin and plectranthone exhibited marked growth inhibition on both cell lines in a time- and dose-dependent manner with minimal cytotoxicity against normal breast cells (HB2). The terpenes even showed superior activities to the tested standards. Flow cytometry showed apoptosis induction and alteration in the cell cycle in colorectal cancer cells treated with both compounds. Nevertheless, it was also found that both compounds inhibited NF-κB transcriptional activity, induced mitochondrial membrane potential depolarization and increased the percentage of reactive oxygen species in the treated cancer cells in a dose-dependent manner as well. Since the anticancer effect of psiadin on cancer cells was higher than that produced by plectranthone, only psiadin was tested to determine its possible targets. The results suggested a high degree of specificity of action affecting particular cellular processes in both cancer cells. In conclusion, both terpenes, in particular psiadin, showed significant discriminative therapeutic potential between cancer and normal cells, a value that is missing in current chemotherapies.