Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer

Abstract

Endometrial cancer is the most common gynecologic cancer in the United States and its incidence and mortality has been rising over the past decade. Few treatment options are available for patients with advanced and recurring endometrial cancers. Novel therapies, which are frequently toxic, are difficult to establish in this patient population which tends to be older and plagued by comorbidities such as diabetes mellitus and hypertension. Therefore, novel, non-toxic therapies are urgently needed. Megestrol acetate is a frequently used drug in endometrial cancer patients. However, its response rate is only 20–30%. To enhance the activity of megestrol acetate in endometrial cancer patients, we explored the potential of combining natural supplements with megestrol acetate and found that the addition of the natural phenolic compound, pterostilbene, to megestrol acetate resulted in a synergistic inhibition of cancer cell growth in vitro and an enhanced reduction of tumor growth in a xenograft mouse model. In addition, dual treatment led to attenuation of signaling pathways, as well as cell cycle and survival pathways. Our results demonstrated for the first time that the anti-tumor activity of megestrol acetate can be enhanced by combining with pterostilbene, providing an insight into the potential application of pterostilbene and megestrol acetate combination for the treatment of endometrial cancer.

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…Similarly, in a athymic nude mouse model of diffuse large B-cell lymphoma, pterostibene (30 mg/kg) markedly inhibited tumor growth, reduced MMP, increased cellular apoptotic index and ROS levels, leading to S-phase arrest in the cell cycle (Kong et al, 2016). More importantly, it was demonstrated that pterostilbene (30 mg/kg) with megestrol acetate (10 mg/kg) significantly reduced HEC-1A tumor growth in an endometrial cancer xenograft mouse model as compared to pterostilbene or megestrol acetate alone (Wen et al, 2017). At in vitro level, the above combination suppressed ERK and STAT3 signaling pathways and estrogen receptor expression.…”

Stilbenoid‐Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor

“…Herein, we were investigating polyphenols from stilbenoid class, such as RSV and its natural dimethylated analog PTS, and their epigenetic effects in breast cancer cells. Stilbenoids were shown to exert anti‐cancer effects in cell lines and in vivo models, however, without a clear molecular mechanism demonstrated . There are a few reports by us and others on the involvement of epigenetics and specifically DNA methylation in the action of stilbenoids .…”

“…Certain dietary constituents have been shown to exert beneficial effects in cancer, including polyphenols from grapes and blueberries, namely resveratrol (RSV) and its dimethylated analog pterostilbene (PTS) . These compounds were shown to have anti‐cancer properties; however, studies to date have been exploratory and limited without direct mechanistic input .…”

Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway

“…Western blots were performed as described previously [ 27 ]. Cells were grown in complete medium overnight and treated with DMSO or pterostilbene at various concentrations.…”

“…In contrast, pterostilbene (PTE), a natural, dimethylated resveratrol analog with higher bioavailability, has recently become of increasing interest [ 15 , 16 , 17 , 18 ]. Its strong antitumor activity, low toxicity, and commercial availability as well as its low cost, has rendered PTE as an attractive agent for adjuvant therapy in malignancies [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. As healthcare costs rise, interest in natural supplements with strong anti-tumor properties has increased, and pterostilbene represents an appealing novel therapeutic agent in chronic cancers such as ovarian cancer, where recurrent disease is common, and long-term goals include maintenance of quality of life along with longevity.…”