Vernonia calvoana Shows Promise towards the Treatment of Ovarian Cancer

Abstract

The treatment for ovarian cancers includes chemotherapies which use drugs such as cisplatin, paclitaxel, carboplatin, platinum, taxanes, or their combination, and other molecular target therapies. However, these current therapies are often accompanied with side effects. Vernonia calvoana (VC) is a valuable edible medicinal plant that is widespread in West Africa. In vitro data in our lab demonstrated that VC crude extract inhibits human ovarian cancer cells in a dose-dependent manner, suggesting its antitumor activity. From the VC crude extract, we have generated 10 fractions and VC fraction 7 (F7) appears to show the highest antitumor activity towards ovarian cancer cells. However, the mechanisms by which VC F7 exerts its antitumor activity in cancer cells remain largely unknown. We hypothesized that VC F7 inhibits cell proliferation and induces DNA damage and cell cycle arrest in ovarian cells through oxidative stress. To test our hypothesis, we extracted and fractionated VC leaves. The effects of VC F7 were tested in OVCAR-3 cells. Viability was assessed by the means of MTS assay. Cell morphology was analyzed by acridine orange and propidium iodide (AO/PI) dye using a fluorescent microscope. Oxidative stress biomarkers were evaluated by the means of lipid peroxidation, catalase, and glutathione peroxidase assays, respectively. The degree of DNA damage was assessed by comet assay. Cell cycle distribution was assessed by flow cytometry. Data generated from the MTS assay demonstrated that VC F7 inhibits the growth of OVCAR-3 cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VC F7-treated cells. Data obtained from the AO/PI dye assessment revealed morphological alterations and exhibited characteristics such as loss of cellular membrane integrity, cell shrinkage, cell membrane damage, organelle breakdown, and detachment from the culture plate. We observed a significant increase (p < 0.05) in the levels of malondialdhyde (MDA) production in treated cells compared to the control. A gradual decrease in both catalase and glutathione peroxidase activities were observed in the treated cells compared to the control. Data obtained from the comet assay showed a significant increase (p < 0.05) in the percentages of DNA cleavage and comet tail length. The results of the flow cytometry analysis indicated VC F7 treatment caused cell cycle arrest at the S-phase checkpoint. Taken together, our results demonstrate that VC F7 exerts its anticancer activity by inhibiting cell proliferation, inducing DNA damage, and causing cell cycle arrest through oxidative stress in OVAR-3 cells. This finding suggests that VC F7 may be a potential alternative dietary agent for the prevention and/or treatment of ovarian cancer.

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

“…The anticancer and antioxidant activities of phytochemical extracts of VA have been established in different scientific studies [124][125][126]. Scientific studies demonstrated that phytochemical extracts of VA and other Vernonia species, including Vernonia calvonia, Vernonia divaricate, Vernonia amygdalina Delile, and Vernonia guineensis Benth, exhibit anticancer activities and are valuable sources for drug-like active natural compound screening [127][128][129][130]. The major identified phytochemicals of VA responsible for its ethnobotanical uses include flavonoids, alkaloids, saponins, terpenes, ligands, cournarins, phenolic acids, sesquiterpenes, and edotides [131][132][133][134].…”

“…The anticancer activities of VA have been studied in various cancer cell lines. We demonstrated in our research laboratory that Vernonia amygdalina inhibited the proliferation of breast cancer (MCF-7) cells [139], Vernonia amygdalina Delile inhibited the growth of prostate cancer (PC-3) cells [128], and Vernonia calvonia caused growth arrest of ovarian cancer (OVCAR-3) cells [127]. Cheng et al demonstrated that VA induced anti-cancer effects in MCF-7 and MDA-MB-231 cells via caspase-dependent and p53-independent pathways [140].…”

Genus Vernonia (Asteraceae): A Promising Source of Antitumor Agents with Pharmacological Potentials

“…Sesquiterpene lactones [42], flavonoids [3], steroids [43], and polysaccharides [33] have been detected in preparations from different species of Vernonia, and several biological activities were reported, including antitumor activity. "The anticancer property of these compounds has attracted a great deal of interest and extensive research studies have been carried out to characterize the anticancer activity, the molecular mechanisms, the chemopreventive potential and the chemotherapeutic application of these compounds" [3,44,45]. Studies focusing on anticancer activity of Vernonia species are summarized in Table 1.…”

“…The results obtained in the studies by Mbemi et al [3] demonstrated that "Vernonia calvoana (VC) fraction 7 significantly reduced the percentage of live cells in a dose-dependent manner, suggesting its antiproliferative effect against ovarian cancer (OVCAR-3) cells. Other Vernonia species including V. divaricata and V. amygdalina act as potential anticancer agents that inhibit the proliferation of breast cancer cells, human leukemia (HL-60) cells, breast (MCF-7) cells and prostate (PC-3) cells" [11,43].…”

“…Cancer is the foremost cause of deaths around the world, and the expectation from 2040 is that there will be a 47% increase cancer cases, due to risk factor associated with globalization and a growing economy [1]. "Usually, the cancer therapy is based in radiotherapy and chemotherapy, and are accompanied from side effects such as nauseous, vomits, loss of appetite, infertility, acute and chronic renal insufficiency and electrolytes disturbances" [2,3]. "The multiple drug resistance (MDR) in chemotherapy is other big problem in cancer treatment, a phenomenon where by tumors that acquire resistance to one type of therapy are resistant to several other drugs, that are often quite different in both structure and mode of action" [4][5].…”