Psiadin and Plectranthone Selectively Inhibit Colorectal Carcinoma Cells Proliferation Via Modulating Cyclins Signaling and Apoptotic Pathways

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2021 Jun 4

PMID 34086816

Citations 1

Authors

Khaled Y Orabi

Mohamed S Abaza

Yunus A Luqmani

Rajaa Al-Attiyah

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Phytochemical analysis, antioxidant activity, and cytotoxic effects of Caulerpa lentillifera extracts inducing cell apoptosis and sub-G/G0-G1 cell cycle arrest in KON oral cancer cells.

Manmuan S, Sirirak T, Tubtimsri S, Petchsomrit A, Chuenbarn T BMC Complement Med Ther. 2025; 25(1):101.

PMID: 40069755 PMC: 11899751. DOI: 10.1186/s12906-025-04835-9.

Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.

Guilz N, Ahn Y, Fatima H, Pedroza L, Seo S, Soni R J Immunol. 2024; 213(1):40-51.

PMID: 38809096 PMC: 11824913. DOI: 10.4049/jimmunol.2300843.

An Anticancer Activity Evaluation of (Roxb.) Bosser Leaves' Extract and its Metabolite Profile.

Razali S, Yuhainis Firus Khan A, Khatib A, Ahmed Q, Abdul Wahab R, Zakaria Z Front Pharmacol. 2021; 12:741683.

PMID: 34721030 PMC: 8548635. DOI: 10.3389/fphar.2021.741683.

References

Cragg G, Pezzuto J . Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. Med Princ Pract. 2015; 25 Suppl 2:41-59. PMC: 5588531. DOI: 10.1159/000443404. View

Jonville M, Kodja H, Humeau L, FOURNEL J, De Mol P, Cao M . Screening of medicinal plants from Reunion Island for antimalarial and cytotoxic activity. J Ethnopharmacol. 2008; 120(3):382-6. DOI: 10.1016/j.jep.2008.09.005. View

Yoon J, Gores G . Death receptor-mediated apoptosis and the liver. J Hepatol. 2002; 37(3):400-10. DOI: 10.1016/s0168-8278(02)00209-x. View

Adhami V, Aziz M, Reagan-Shaw S, Nihal M, Mukhtar H, Ahmad N . Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery. Mol Cancer Ther. 2004; 3(8):933-40. View

Sun S, Hail Jr N, Lotan R . Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 2004; 96(9):662-72. DOI: 10.1093/jnci/djh123. View

Lee J, Koo T, Hwang B, Lee J . Kaurane diterpene, kamebakaurin, inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-kappa B target genes. J Biol Chem. 2002; 277(21):18411-20. DOI: 10.1074/jbc.M201368200. View

Karin M . Nuclear factor-kappaB in cancer development and progression. Nature. 2006; 441(7092):431-6. DOI: 10.1038/nature04870. View

Mahadeo K, Grondin I, Kodja H, Soulange Govinden J, Laulloo S, Frederich M . The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2017; 210:48-68. DOI: 10.1016/j.jep.2017.08.023. View

Chen W, Li Z, Bai L, Lin Y . NF-kappaB in lung cancer, a carcinogenesis mediator and a prevention and therapy target. Front Biosci (Landmark Ed). 2011; 16(3):1172-85. PMC: 3032584. DOI: 10.2741/3782. View

10.

Zhong Z, Chen X, Tan W, Xu Z, Zhou K, Wu T . Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis. Eur J Pharmacol. 2011; 667(1-3):50-5. DOI: 10.1016/j.ejphar.2011.03.041. View

11.

Nakano T, Go T, Nakashima N, Liu D, Yokomise H . Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer. Anticancer Res. 2020; 40(2):1007-1014. DOI: 10.21873/anticanres.14035. View

12.

Newman D, Cragg G . Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83(3):770-803. DOI: 10.1021/acs.jnatprod.9b01285. View

13.

Rahman K, Ali S, Aboukameel A, Sarkar S, Wang Z, Philip P . Inactivation of NF-kappaB by 3,3'-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells. Mol Cancer Ther. 2007; 6(10):2757-65. DOI: 10.1158/1535-7163.MCT-07-0336. View

14.

Jonville M, Kodja H, Strasberg D, Pichette A, Ollivier E, Frederich M . Antiplasmodial, anti-inflammatory and cytotoxic activities of various plant extracts from the Mascarene Archipelago. J Ethnopharmacol. 2010; 136(3):525-31. DOI: 10.1016/j.jep.2010.06.013. View

15.

Abaza M, Bahman A, Al-Attiyah R . Valproic acid, an anti-epileptic drug and a histone deacetylase inhibitor, in combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic and chemosensitizing effects in human colorectal cancer cells: underlying molecular.... Int J Mol Med. 2014; 34(2):513-32. DOI: 10.3892/ijmm.2014.1795. View

16.

Fortin H, Vigor C, Lohezic-Le Devehat F, ROBIN V, Le Bosse B, Boustie J . In vitro antiviral activity of thirty-six plants from La Réunion Island. Fitoterapia. 2002; 73(4):346-50. DOI: 10.1016/s0367-326x(02)00080-1. View

17.

Giacinti C, Giordano A . RB and cell cycle progression. Oncogene. 2006; 25(38):5220-7. DOI: 10.1038/sj.onc.1209615. View

18.

Wen Q, Zhan Y, Zheng H, Zang H, Luo J, Zhang Y . Elevated expression of mcl-1 inhibits apoptosis and predicts poor prognosis in patients with surgically resected non-small cell lung cancer. Diagn Pathol. 2019; 14(1):108. PMC: 6788105. DOI: 10.1186/s13000-019-0884-3. View

19.

Govinden-Soulange J, Magan N, Gurib-Fakim A, Gauvin A, Smadja J, Kodja H . Chemical composition and in vitro antimicrobial activities of the essential oils from endemic Psiadia species growing in mauritius. Biol Pharm Bull. 2004; 27(11):1814-8. DOI: 10.1248/bpb.27.1814. View

20.

Perciavalle R, Opferman J . Delving deeper: MCL-1's contributions to normal and cancer biology. Trends Cell Biol. 2012; 23(1):22-9. PMC: 3532576. DOI: 10.1016/j.tcb.2012.08.011. View