Svetlana Hovhannisyan’s research while affiliated with Yerevan State University and other places

The continuous increase in cancer rates, failure of conventional chemotherapies to control the disease, and excessive toxicity of chemotherapies clearly demand alternative approaches. Natural products contain many constituents that can act on various bodily targets to induce pharmacodynamic responses. This study aimed to explore the combined anticancer effects of Rumex obtusifolius (RO) extract and the chemotherapeutic agent 5-fluorouracil (5-FU) on specific molecular targets involved in cancer progression. By focusing on the PI3K/Akt signaling pathway and its related components, such as cytokines, growth factors (TNFa, VEGFa), and enzymes (Arginase, NOS, COX-2, MMP-2), this research sought to elucidate the molecular mechanisms underlying the anticancer effects of RO extract, both independently and in combination with 5-FU, in non-small lung adenocarcinoma A549 cells. The study also investigated the potential interactions of compounds identified by HPLC/MS/MS of RO on PI3K/Akt in the active site pocket through an in silico analysis. The ultimate goal was to identify potent therapeutic combinations that effectively inhibit, prevent or delay cancer development with minimal side effects. The results revealed that the combined treatment of 5-FU and RO demonstrated a significant reduction in TNFa levels, comparable to the effect observed with RO alone. RO modulated the PI3K/Akt pathway, influencing the phosphorylated and total amounts of these proteins during the combined treatment. Notably, COX-2, a key player in inflammatory processes, substantially decreased with the combination treatment. Caspase-3 activity, indicative of apoptosis, increased by 1.8 times in the combined treatment compared to separate treatments. In addition, the in silico analyses explored the binding affinities and interactions of RO's major phytochemicals with intracellular targets, revealing a high affinity for PI3K and Akt. These findings suggest that the combined treatment induces apoptosis in A549 cells by regulating the PI3K/Akt pathway.

In this study, the objective was to explore novel strategies for improving the efficacy of anticancer therapy. The focus was on investigating the antiproliferative effects of combining Rumex obtusifolius extract (RO) with the chemotherapeutic agent 5-Fluorouracil (5-FU) in non-small A549 lung cancer cells (NSCLC). Key factors such as the PI3K/Akt cell signaling system, cytokines, growth factors (TNFa, VEGFa), and enzymes (Arginase, NOS, COX-2, MMP-2) were analyzed to assess the impact of the combination treatment. Results revealed that the combined treatment of 5-FU and RO demonstrated a significant reduction in TNFa levels, comparable to the effect observed with RO alone. RO was found to modulate the PI3K/Akt pathway, influencing the phosphorylated and total amounts of these proteins during the combined treatment. Notably, COX-2, a key player in inflammatory processes, substantially decreased with the combination treatment. Caspase-3 activity, indicative of apoptosis, increased by 1.8 times in the combined treatment compared to separate treatments. In addition, in silico analyses explored the binding affinities and interactions of RO's major phytochemicals with intracellular targets, revealing a high affinity for PI3K and Akt. These findings suggest that the combined treatment induces apoptosis in A549 cells by regulating the PI3K/Akt pathway.

Plants of the genus Alchemilla are well known for their pharmacological effects. Alchemilla smirnovii Juz., also known as lady's mantle possessed high growth-inhibiting properties against cancer cells according to earlier reports. We aimed to explore the anticancer modulatory effect of A. smirnovii extract toward 5-fluorouracil and elucidate the possible mechanism of its cytotoxic action in the HeLa cancer cell model. Synergistic interactions of plant extract with the chemotherapeutic agent were assessed by MTT assay. Based on obtained data the ethanol extract of A. smirnovii exhibits synergistic effects, enhancing the growth-inhibiting properties of 5-fluorouracil when used together. Additionally, the extract leads to a reduction in arginase activity and an elevation in the level of MDA․ This implies that A. smirnovii induces oxidative stress, and can potentially cause apoptosis in cancer cells.

The increase in the incidence of cancer in Armenia and around the world is a serious problem, and the chemical interventions used in cancer therapy, which partially have a therapeutic effect, are often accompanied by the destruction of normal body cells. Therefore, it is necessary to search for new alternative treatments that will be highly effective and accompanied by a small number of side effects. From this point of view, several medicinal plants used in traditional medicine can be considered new, effective means of treating cancer, since they have an immunostimulating effect on individual parts of the human immune system. Considering all this, the work aimed to study the quantitative changes in the production of interleukin-2 in the blood and tumor of rats under the influence of plant extracts in an experimental model of DMBA (7,12-dimethylbenz[a]anthracene)-induced breast cancer, as well as cell cultures of breast cancer and lungs. We showed that Hypericum alpestre and Rumex obtusifolius extracts have a pronounced anticancer effect by increasing interleukin-2 (IL-2) levels in the blood and tumors of rats. They also brought quantitative changes in phosphoinositol-3-kinase (PI3K), which plays a key role in cancer development. This could be the basis for developing new anticancer or cancer-preventing drugs derived from more potent H. alpestre and R. obtusifolius herbs.

Compounds of plant origin are considered promising alternative approaches in the development of medicines for the prevention and treatment of cancer. The large diversity of herbal species still requires careful exploration as a source for new anticancer compounds. The goal of the study was to screen different herbal extracts traditionally used in Armenian folk medicine for their cytotoxic effect against some cancer cell lines, and to find the prospective plant species among them. The cytotoxicity of the plant ethanol extracts was evaluated with MTT test against HeLa (human cervical carcinoma) and A549 (human lung adenocarcinoma) cells. Antioxidant properties were assessed with DPPH free radical scavenging assay. Five of the tested ten herbal extracts exhibited significant growth-inhibiting activity on HeLa cells. Moreover, Alchemilla smirnovii and Hypericum alpestre extracts also showed potent cytotoxicity on human lung adenocarcinoma cells. These two plants possessed high antiradical activity as well. Their DPPH stoichiometric values were 0.4234 and 0.14437 respectively, meaning that 1 µg of plant extract brought the reduction of DPPH equal to the respective stoichiometric values in µg. Thus, A. smirnovii and H. alpestre extracts expressed themselves as potent cytotoxic and antioxidant agents and could have promising anticancer potential. Further evaluation of their in vivo anticancer properties has much interest.