Retracted: Alkannin represses growth of pancreatic cancer cells based on the down regulation of miR‐199a

Abstract

Alkannin displays tumor suppressive activity by initiating apoptosis. Here, we corroborated its role in pancreatic carcinoma (PANC-1) cells and addressed the molecular mechanism in which microRNA-199a (miR-199a) and Klotho might be implicated. PANC-1 and MIN6 cells were treated by alkannin and its role was evaluated in cellular viability. Next we assessed the ability of PANC-1 cells to proliferate, migrate, and invade as well as apoptosis process. Besides, proliferating cell nuclear antigen (PCNA), CyclinD1, p53, and caspases were quantified using Western blot. miR-199a was detected by qRT-PCR. miR-199asilenced or-replenished cells were established to study its function role in Klotho in conjunction with alkannin. Further, Klotho-overexpressed or-silenced cells were constructed to investigate the alteration of mTOR and MEK/ERK pathways. Alkannin repressed the viability of PANC-1 cells instead of MIN6 cells. Alkannin counteracted the growth of PANC-1 cells through inhibiting proliferation, migration, and invasion and facilitating apoptosis, which was evidenced by the modulation on PCNA, CyclinD1, p53, and cleavage of caspases. The silence of miR-199a by alkannin was also involved in the antitumor process. Alkannin enhanced Klotho expression possibly through silencing miR-199a. Besides, mTOR and MEK/ERK signaling were counteracted by Klotho overexpression while facilitated by its silence. Alkannin inhibited the growth of PANC-1 cells via modulating miR-199a-Klotho node. During this process, mTOR and MEK/ERK pathways were blunted. K E Y W O R D S alkannin, Klotho, miR-199a, pancreas carcinoma 1 | INTRODUCTION Worldwide, pancreatic carcinoma is typical of the close parallel between incidence and mortality, with 458,918 new pancreatic cancer cases and 432.242 deaths predicted in 2018. 1 The high mortality is ascribed to multitude factors, of which the most possible is the late stage at which most patients are diagnosed. 2

Alkannin exerts antitumor properties in cutaneous squamous cell carcinoma by inducing apoptosis and shifting the M1/M2 polarization of tumor‐associated macrophages by upregulating PTEN

“…Our study found that alkannin inhibited the activation of AKT signaling by upregulating PTEN. Regarding how alkannin regulates PTEN, previous reports suggested that alkannin reduces the expression levels of some microRNAs, including miR‐4461, miR‐199a, and miR‐9, that have been reported to target PTEN 7,8,23,31–33 . Hence, we speculated that alkannin might regulate PTEN expression through multiple pathways, such as the miRNA–mRNA axis.…”

“…Regarding how alkannin regulates PTEN, previous reports suggested that alkannin reduces the expression levels of some microRNAs, including miR-4461, miR-199a, and miR-9, that have been reported to target PTEN. 7,8,23,[31][32][33] Hence, we speculated that alkannin might regulate PTEN expression through multiple pathways, such as the miRNA-mRNA axis. The detailed mechanism of alkannin in CSCC needs to be clarified by performing more in-depth experiments in the future.…”

“…Wang et al revealed that alkannin curbed ovarian cancer cell growth, migration, and invasion but induced apoptosis by modulating miR‐4461 7 . In addition, Zhang et al confirmed that alkannin suppressed pancreatic carcinoma cell viability, proliferation, and metastasis while facilitating apoptosis by reducing the content of miR‐199a 8 . Moreover, alkannin prominently blocked cell growth and metastasis in glioma by modulating the IQGAP/mTOR signaling pathway 9 .…”

Alkannin Inhibits the Development of Ovarian Cancer by Affecting miR-4461

“…Curcumin inhibited prostate cancer progression by regulating the miR-30a-5p/PCLAF axis [ 15 ]. In addition, alkannin has been found to inhibit the growth of pancreatic cancer cells by downregulating miR-199a [ 16 ]. Here, the interaction between alkannin and miR-4461 was investigated in OC.…”

A new synthetic method toward a key intermediate in the total synthesis of alkannin and shikonin

“…These compounds show a wide range of significant pharmacological activities, such as antibacterial, 2 anti-inflammatory, 3 antifungal, 4 and antitumor. [5][6][7][8] Many methodologies on their total synthesis have been described. [9][10][11][12] Nicolaou 13 reported a concise and efficient total synthesis of alkannin and shikonin, in which a novel protecting system for the masking of 5,8-dihydroxy-1,4-naphthoquinones was used and 4-methyl-1-(naphtho[1,8-de:4,5-d'e'] bis( [1,3]dioxine)-4-yl)pent-3-en-1-one (5) (Scheme 1) served as a key intermediate.…”