Inhibition of cell proliferation by mild hyperthermia at 43°C with Paris Saponin I in the lung adenocarcinoma cell line PC-9

Abstract

Abstract. Rhizoma paridis is widely used for cancer therapy due to its potential involvement in the suppression of tumor growth. However, at present there is no clear explanation for the mechanism underlying the inhibitory effects of Rhizoma paridis combined with hyperthermia on tumor growth. The aim of the present study was to evaluate the effects of Paris saponin I (PSI) combined with hyperthermia on a variety of non-small cell lung cancer (NSCLC) cell lines. An MTT assay was used to determine the levels of growth inhibition. The cell cycle was analyzed using flow cytometry and cell apoptosis was analyzed with Annexin V/propidium iodide staining and the Hoechst assay. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 proteins were detected using western blotting. The inhibition rates significantly increased with PSI in combination with hyperthermia at 43˚C. PSI with hyperthermia at 43˚C caused G2/M phase arrest and significantly induced apoptosis. The expression level of Bcl-2 decreased, while Bax expression increased following treatment with PSI with hyperthermia at 43˚C. In addition, the protein expression of caspase-3 was significantly enhanced. PSI combined with hyperthermia is a potent antitumor treatment through the inhibition of proliferation of NSCLC cells and may be developed as a new antitumor therapy. PSI combined with hyperthermia significantly induced apoptosis through a multi regulatory process involving G2/M arrest and regulation of Bax, Bcl-2 and caspase-3 expression, resulting in cell death and tumor inhibition.

Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis

“…Thus, developing effective agents to sensitize Cisplatin efficacy and overcome platinum resistance in gastric cancer makes a challenge. Paris saponin I, originally derived from Rhizoma paridis, which is the root of Chinese herbal, has been recently investigated as a new anticancer agent [14–19]. In the present study, we demonstrated that PSI sensitized gastric cancer cells to Cisplatin with low toxicity.…”

“…The major advantages of PSI as an anticancer agent are related to its ability to inhibit tumor growth in various cancer types [14–19] associated with a low level of toxicity. Recent studies have demonstrated that PSI possesses pharmacological activities concerning the cytotoxic activity against many cancers with mechanism of increasing levels of Bax, cytochrome c, activating caspases, and by decreasing both Bcl-2 expression and specific kinase-1/2 activity [14–19]. PSI may be a potential anticancer drug by inhibiting proliferation and a good radiosensitizer of gefitinib resistant NSCLC cells [20,21].…”

Simple Trans-Platinum Complex Bearing 3-Aminoflavone Ligand Could Be a Useful Drug: Structure-Activity Relationship of Platinum Complex in Comparison with Cisplatin

“…In the present study, cytostatics with hyperthermia induced apoptosis in ovarian cancer cells OVCAR-3 and Caov-3 by increasing the expression of BAX and CASP3 and reducing the expression of BIRC5. Many studies currently analyse the effects of elevated temperatures on cell survival in a cytostatic environment [71][72][73]. As a result, the expression of survivin and induction of apoptosis is reduced.…”

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

“…Developing new treatments is necessary in order to improve the prognosis for NSCLC patients. Traditional Chinese Medicine is believed by some to be beneficial in anticancer treatment and in reducing the side effects of conventional treatment (3)(4)(5)(6)(7)(8)(9).…”

“…The mechanisms of hyperthermia in treating cancers may be related to inhibiting DNA repair, promoting intracellular accumulation of chemical agents, altering cellular Ca 2+ homeostasis, inducing cell cycle arrest and apoptosis, increasing membrane permeability and rearranging the cytoskeleton (26)(27)(28). Hyperthermia also has direct cytotoxic effects, which provide a number of other clinical advantages, including activation of the immune system against tumors, improvement of oxygenation and enhancing drug delivery (29)(30)(31)(32). However, the underlying mecha nisms associated with its efficacy are largely unknown.…”