The Potential Anti-Osteosarcoma Activity from Naturally Extracted Phenolic Compound: A Scoping Review

Abstract

Chemotherapy is the standard treatment component for osteosarcoma alongside the surgery. Nevertheless, the survival rate of patients diagnosed with osteosarcoma has not changed over the past three decades. Phenolic compounds are widely reported for having anti-proliferative effects against various cancers including osteosarcoma. Based on the framework published by Arskey and O’Malley [1] this scoping review was conducted to map the published literature on the anti-osteosarcoma activity of the phenolic compounds.
 
 Initially, a literature search was conducted from electronic databases like PubMed, Scopus, EBSCO, Google Scholar Science Direct, and Web of Science. Articles on anti-osteosarcoma activities of phenolic compounds that were published between January 2001 and May 2022 were retrieved. The review process was guided by the framework of systematic reviews and meta-analysis (PRISMA) [2]. 
 
 In total, 3168 articles were retrieved from the literature search. After a thorough screening, 95 articles were included in the final analysis after met the inclusion criteria. Most of the studies were published between the year 2011 to 2022 (84.2%) and only a few were published between 2001 to 2010 (15.8%) (Table 1). Among the selected studies, 53 types of phenolic compounds were identified to have a promising anti-osteosarcoma activity. Curcumin (12.6%) was the most reported phenolic compound followed by quercetin (11.6%) and resveratrol (10.5%) (Table 2). All studies were utilised in-vitro studies (n = 95), and some also conducted in-vivo evaluations (n = 17). MG-63 (50.5%) was identified to be the most used cell line. Meanwhile, BALB/c nude mice (58.8%) was the most frequently used in the in-vivo evaluation. In this review, it was found that 13 studies analysed the combination between phenolic compounds and chemotherapeutic drugs with 53.8% of the analysis demonstrating synergistic effect.
 The number of published articles on the anti-osteosarcoma activities of phenolic compounds has increased dramatically over the past 10 years. Phenolic compounds became the main choice in oncotherapy research as it represents a major secondary metabolite in the plant. In this review, all the selected articles utilised in-vitro studies, and only several studies conducted in-vivo evaluations. For the in-vitro study, MG-63 was most frequently used because this cell line was reported to have phenotypic stability [3]. For the in-vivo study, BALB/c nude mice was mostly used because the utilization of immunocompromised mice has become an essential tool in the drug evaluation for cancer to maintain the tumour pathological traits [4]. Even though most of the compounds showed a remarkable inhibitory effect in-vitro and in-vivo, no clinical trial study was reported. Combination analysis is one of the efforts to induce the effectiveness of the treatment. Seven studies reported the synergistic effect when phenolic compound was combined with chemotherapeutic drug. The synergistic effect is the most desired drug-drug interaction in the application of the combination treatment as it can induce treatment efficacy [5]. 
 
 In conclusion, this scoping review indicated a significant increase in the evaluation of the anti-osteosarcoma activity of the phenolic compounds. Yet, several research gaps are remaining to be investigated like combination analysis and further continuation of clinical trial study so that the development of phenolic compound-based drugs for osteosarcoma treatment can be realised soon.