All tumors originating from glial cells are gliomas commonly affecting the body's central nervous system. According to the World Health Organization, gliomas are classified according to their presumed cell of origin as astrocytic tumors: astrocytoma grade I, astrocytoma grade II, astrocytoma grade III (anagal astrocytoma), astrocytoma IV (glioblastoma or GM), oligodendrogliomas, ependymomas and mixed gliomas (1, 2). Glioblastoma is the most common, lethal and damaging type of primary brain tumor in humans and is characterized by an unavoidable propensity to relapse and poor prognosis (3, 4). Glioblastoma accounts for 42% of all central nervous system tumors and 60% of all brain tumors in adults, with a median survival of 15 months (5, 6).
Glioblastoma multiforme (GBM) has no cure, and intertumoural or intratumour heterogeneity is one of the hallmarks of this cancer. The development of GBM is characterized by age, sex, race, genetic disorders, and ionizing radiation (7). In GBM, cellular heterogeneity is associated with therapeutic and drug resistance due to an array of genetic alterations involved in the control of cell cycle kinetics, cell growth, apoptosis, cell invasion and neovascularization (8, 9). Despite surgical resection, irradiation and adjuvant chemotherapy, GBM remains a major therapeutic problem, as survival following diagnosis can reach 12 to 15 months, with less than 5% survival longer than five years (8).
The clinical treatment of GBM has not been successful despite the knowledge and advances in understanding the associated complex biology. The genetic and epigenetic heterogeneity of GBM has helped but has not been fully translated to effective clinical (10) outcomes. Some conventional DNA-damaging anticancer drugs have failed in GBM, showing proven efficacy in other cancer types and hence limiting the treatment options for GBM. Hence, the failure of these agents necessitates the development of new drugs and new categories of therapeutics. Temozolomide (TMZ) was approved for GBM treatment for the first time, just as bevacizumab is used to treat recurrent GBM and was approved by the Food and Drug Administration. (11, 12). Bevacizumab nitrosoureas and TMZ, which are the second-line agents, are the most common systemic agents for recurrent high-grade gliomas (HGGs), but there is no superiority of these agents over one another. Despite standard treatment and care centered on surgical resection, chemotherapy and radiation therapy, patients have a poor progression-free survival (PFS) of 7–8 months, a median survival of 14–16 months and a 5-year overall survival (OS) of 9.8% (13–15).
Natural plant products, which possess similar molecular targets as pharmaceutical drugs in cancer treatment, remain an invaluable source of active components with therapeutic efficacy. Over 3000 medicinal plant species, with less than 10% of these species being analyzed for major bioactive molecules, are being used in cancer treatment (16). Compared with synthetic organic molecules, bioactive medicinal plants exhibit high potential and capacity for use in mechanism-based strategies. Curcumin, etoposide, camptothecin, and paclitaxel are plant-derived antineoplastic compounds that can effectively disrupt tumorigenic cell growth via apoptosis and inhibition of cancer cell proliferation.
The Lamiaceae family includes an herbaceous perennial shrub called Hoslundia opposita Vahl (H. opposita) that is characteristically round and yellowish or orange. It is well distributed in tropical and subtropical lands of Africa (17), including Nigeria. Ethnobotanical use includes the treatment of various ailments, such as colds, sore throat, gonorrhea, convulsion, stomach pains, ringworms, parasitic skin infection, snake bites, and mental disorders (18, 19). Scientific investigations have confirmed the antidiabetic, antispasmodic, expectorant, antimicrobial, anti-inflammatory and antibacterial effects of H. pylori (18, 20, 21). The reported anticancer activities of H. opposita in some cell lines, including human breast adenocarcinoma MCF-7 (ATCC No. HTB-22), BT-20 (ATCC No. HTB-19), and BT-549 (ATCC No. HTB-122); prostate adenocarcinoma PC-3 (ATCC No. CRL-1435); acute T-cell leukemia Jurkat (ATCC No. TIB-152); colon adenocarcinoma SW-480 (ATCC No. CCL-228) cells; and rhabdomyosarcoma cancer (22, 23), are scant. Furthermore, no anticancer effects of H. opposita have been reported on GBM. In the present study, the cytotoxic, clonogenic, apoptotic, and reactive oxygen species effects and mitochondrial membrane potential of the crude extract and fractions of H. opposites were profiled in vitro in GBM cells. The results from these in vitro studies can be expanded upon in the future in animal models.