Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway

Suresh Mickymaray; Faiz Abdulaziz Alfaiz; Anand Paramasivam; Vishnu Priya Veeraraghavan; Nanthini Devi Periadurai; Krishna Mohan Surapaneni; Guangfeng Niu

doi:10.1016/j.sjbs.2021.05.006

Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway

Saudi J Biol Sci. 2021 Jul;28(7):3641-3649. doi: 10.1016/j.sjbs.2021.05.006. Epub 2021 May 8.

Authors

Suresh Mickymaray¹, Faiz Abdulaziz Alfaiz¹, Anand Paramasivam², Vishnu Priya Veeraraghavan³, Nanthini Devi Periadurai⁴, Krishna Mohan Surapaneni⁵, Guangfeng Niu^{6

7}

Affiliations

¹ Department of Biology, College of Science, Al-Zulfi, Majmaah University, Riyadh Region, Majmaah 11952, Saudi Arabia.
² Department of Basic Medical Sciences, College of Dentistry, Al-Zulfi, Majmaah University, Riyadh Region, Majmaah 11952, Saudi Arabia.
³ Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, India.
⁴ Departments of Microbiology, Molecular Virology and Hospital Infection Control, Panimalar Medical College Hospital & Research Institute, Varadharajapuram, Poonamallee, Chennai 600 123, India.
⁵ Department of Biochemistry, Panimalar Medical College Hospital & Research Institute, Varadharajapuram, Poonamallee, Chennai 600 123, India.
⁶ Department of Orthopaedics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwu Weiqi Road, Jinan, Shandong 250021, China.
⁷ Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong 250021, China.

Abstract

Osteosarcoma is the frequent pediatric bone cancer where pediatric osteosarcoma incidences are more than 10% within the population. Most of the patients with osteosarcoma fall within the age of 15-30 years. Therefore, in this research, we examined the anticancer effect of Rhaponticin against the human osteosarcoma (MG-63) cells. The cytotoxicity of Rhaponticin on the MC3T3-E1 and MG-63 cells was examined through the MTT assay. The intracellular ROS accumulation, cell nuclear morphological alterations, apoptotic cell death and nuclear damages, and MMP status of Rhaponticin administered MG-63 cells were inspected by fluorescent staining techniques. The cell migration was assessed through scratch assay. The mRNA expressions of PI3K-Akt-mTOR signaling proteins were studied by RT-PCR analysis. Rhaponticin showed potent cytotoxicity, substantially inhibited the MG-63 cell growth, and displayed morphological alterations. However, rhaponticin did not affect the MC3T3-E1 cell viability. Rhaponticin administered MG-63 cells demonstrated augmented intracellular ROS accretion, weakened MMP, increased nuclear damages, and increased apoptosis. Rhaponticin effectively down-regulated the PI3K-Akt-mTOR signaling cascade in the MG-63 cells. These outcomes proved that the Rhaponticin can be a hopeful chemotherapeutic agent in the future to treat human osteosarcoma.

Keywords: Apoptosis; MG-63 cells; Osteosarcoma; PI3K-Akt-mTOR pathway; Rhaponticin.