Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladd
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Cancer Cell International Open Access
REVIEW
Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer Khushbukhat Khan1, Cristina Quispe2, Zeeshan Javed3, Muhammad Javed Iqbal4, Haleema Sadia5, Shahid Raza3, Asma Irshad6, Bahare Salehi7*, Željko Reiner8 and Javad Sharifi‑Rad9*
Abstract Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male pop‑ ulation. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasive‑ ness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different pos‑ sible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabili‑ ties. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer. Keywords: mTOR, miRNAs, Biomarkers, Natural therapeutic, Drug resistance Introduction Bladder cancer (BC) is among the nine most prevalent types of cancer globally [1]. The male population is mostly affected by this severe disease as BC is among the seventh most common cancers in males. BC accounts for 165,000 deaths annually, and approximately 430,000 cases are reported each year worldwide [2, 3]. In US alone bladder cancer has been responsible for more than 17,240 deaths in the year 2018 and rate of incidence is increasing suggesting that more and more men are suffering from this disease due to occupational exposure to carcinogens *Correspondence: [email protected]; [email protected]; [email protected]; [email protected] 7 Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 9 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article
and smoking. Men in the United States are nearly four times more likely to be diagnosed with BC than women and approximately 1 in 27 men in the United States will develop BC in their lifetime. However, in some regions, mortality associated with BC is more frequent in females [2]. The incidence of BC is comparatively less in Asian countries but high mortality rate of BC is reported in Western Asia [4]. BC is a multifaceted disease [5]. The clinical manifestations associated with BC are underpinned by the complex molecular land
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