Combinational Use of Phytochemicals and Chemotherapeutic Drugs Enhance Their Therapeutic Potential on Human Cervical Cancer Cells

Abstract

Background: The negative side effects of chemotherapeutic drugs have led to the need to identify safer therapeutics. A wide array of epidemiological and experimental data encourages the use of dietary agents to impede or delay different stages of cancer. Well tolerated lower doses of individual agents can be effectively employed if there is therapeutic synergy; thereby minimizing the side effects and enhancing successful outcome. However, a variety of interactions are possible when different agents are used in combination, therefore, dietary agents alone or in combination with chemotherapeutic agents must be thoroughly studied before considering them for clinical settings. Objectives: This study was designed to determine the interaction of two phytochemicals (quercetin, sulforaphane) with each other as well as with established chemotherapeutic drugs, like cisplatin and 5-fluorouracil. Methods: Cell viability assay, cell cycle analysis, and scratch wound assay were performed to understand their combined impact on proliferation and metastasis of HeLa cells. Further, combination index (CI) was calculated to identify the type of interaction between the tested compounds concurrently. Results: Concurrent administration of sublethal doses of the phytochemicals with chemotherapeutic drugs resulted in augmented anti-proliferative potential evidenced in elevated cytotoxicity, apoptosis induction, and inhibition of migration. Combination index was < 1 and indicated synergy between the tested compounds. Conclusions: Combination of these compounds can help to develop cancer treatment better.

Co-administration of Chrysin and Luteolin with Cisplatin and Topotecan Exhibits a Variable Therapeutic Value in Human Cancer Cells, HeLa

“…In previous studies from our lab, the IC50 value was found to be 1.25 and 5 μM (data published) for topotecan and cisplatin, respectively. 2,50 Similarly, based on our previous studies, the IC50 values of chrysin and luteolin are 15 and 20 μM, respectively. 20,33 The sublethal concentrations were used for these agents based on previous studies at our lab.…”

“…The experiment was performed in triplicate, and the average is the effect of the drugs in combination and to determine the drug interaction as described in our previous combination study. 2 The formula used to calculate CI is as follows…”

Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways

“…Similarly, binding of EGCG to HDAC4 was found to overlap well with the co-crystallized inhibitors EBE (PDB ID: 6FYZ), TFG (PDB ID: 2VQJ), 9F4 (PDB ID: 4CBT) and HA3 (PDB ID: 2VQM). Suppression of HDACs reverses TSG silencing, lessens growth and induces apoptosis (Sundaram et al 2019a).…”

“…Nevertheless, currently identified drugs have been shown to be toxic with low specificity. Several studies have demonstrated the anti-cancer effect of dietary bioactive compounds, resulting in apoptosis, transcriptional modulation of molecular targets and potentiation of chemotherapeutic drugs (Kedhari Sundaram et al 2019b;Sundaram et al 2019a). Their anticarcinogenic ability has also been ascribed to their capacity to influence the epigenetic machinery and reestablish TSG transcription (Sundaram et al 2017;Kedhari Sundaram et al 2019a).…”

Nanodelivery of natural isothiocyanates as a cancer therapeutic

“…There is a growing interest in natural compounds such as natural ITCs, which could be used together with conventional chemotherapeutic drugs in combination therapy. It has been reported by many studies that the combinational use of natural ITCs and other anti-cancer agents could achieve synergistic anti-cancer activity [78][79][80][81][82]. In a recent review, Kamal at al.…”