Inhibition of human prostate cancer (PC-3) cells and targeting of PC-3-derived prostate cancer stem cells with koenimbin, a natural dietary compound from <em>Murraya koenigii</em> (L) Spreng

Abstract

BackgroundInhibition of prostate cancer stem cells (PCSCs) is an efficient curative maintenance protocol for the prevention of prostate cancer. The objectives of this study were to assess the efficiency of koenimbin, a major biologically active component of Murraya koenigii (L) Spreng, in the suppression of PC-3 cells and to target PC-3-derived cancer stem cells (CSCs) through apoptotic and CSC signaling pathways in vitro.Materials and methodsThe antiproliferative activity of koenimbin was examined using MTT, and the apoptotic detection was carried out by acridine orange/propidium iodide (AO/PI) double-staining and multiparametric high-content screening (HCS) assays. Caspase bioluminescence assay, reverse transcription polymerase chain reaction (RT-PCR), and immunoblotting were conducted to confirm the expression of apoptotic-associated proteins. Cell cycle analysis was investigated using flow cytometry. Involvement of nuclear factor-kappa B (NF-κB) was analyzed using HCS assay. Aldefluor™ and prostasphere formation examinations were used to evaluate the impact of koenimbin on PC-3 CSCs in vitro.ResultsKoenimbin remarkably inhibited cell proliferation in a dose-dependent manner. Koenimbin induced nuclear condensation, formation of apoptotic bodies, and G0/G1 phase arrest of PC-3 cells. Koenimbin triggered the activation of caspase-3/7 and caspase-9 and the release of cytochrome c, decreased anti-apoptotic Bcl-2 and HSP70 proteins, increased pro-apoptotic Bax proteins, and inhibited NF-κB translocation from the cytoplasm to the nucleus, leading to the activation of the intrinsic apoptotic pathway. Koenimbin significantly (P<0.05) reduced the aldehyde dehydrogenase-positive cell population of PC-3 CSCs and the size and number of PC-3 CSCs in primary, secondary, and tertiary prostaspheres in vitro.ConclusionKoenimbin has chemotherapeutic potential that may be employed for future treatment through decreasing the recurrence of cancer, resulting in the improvement of cancer management strategies and patient survival.

Influence of Geographical and Seasonal Variations on Carbazole Alkaloids Distribution in Murraya koenigii: Deciding Factor of Its In Vitro and In Vivo Efficacies against Cancer Cells

“…We have earlier compared the degree of apoptosis between mahanine and mahanimbine in lymphoblastic leukemia, myeloid leukemia, glioma, pancreatic, lung, colorectal, and cervical cancers cells [4]. Koenimbine reduced metabolic activity of prostate cancer [15], breast cancer [16], and liver cancer cells [17]. However, the biological activity of mahanimbine and koenimbine was not tested in ovarian cancer cells.…”

Anti-Cancer and Acute Toxicity Activity of Benzo[e]Indol-2- Ylidene)-3 -(4-Methoxyphenyl) Imino Propanal

“…Many carcinogenicmaerial as natural and synthetic compounds were demonstrated in previous studies to enhance chemoresistance and tumorigenesis through cell cycle dysregulation and apoptosis inhibition in cancer cell [23], [24] . Like Koenimbin was induced PC3 cell cycle arrest with high percentage in the G0/G1 phase that revealed to inhibition of cellular proliferation through G0/G1 phase arrest [19] .Generation of ROS interact with DNA caused alteration of the cell cycle phase [25] . DNA damage, and cell cycle perturbations induced by two representative gold(III) complexes in human leukemic cells with different cisplatin sensitivity [26] .This made 2P effect on the disturb DNA lead to PC3 cell cycle arrest.…”

“…A study gives a first prove in vivo that α-tomatine has antitumor affection of human androgen-independent prostate cancer(PC-3) cell line, potentially advantages was to prevention, thus acting as a therapy will need for more investigation [18] . A Natural dietary compound koenimbin reported as inhibitor of human prostate cancer, targeting PC-3-derived prostate cancer stem cells with koenimbin remarkably by induced nuclear condensation, forming of apoptotic bodies, and G0/G1 phase arrest of PC-3 cells [19] .…”

Nutritive Importance and Therapeutics Uses of Three Different Varieties (Murraya koenigii, Micromelum minutum, and Clausena indica) of Curry Leaves: An Updated Review

“…One possible mechanism of koenimbine in apoptosis in breast cancer cells could be the downregulation of the Wnt/ β -catenin self-renewal pathways. Similarly, koenimbine has remarkably inhibited cell proliferation of prostate cancer stem cells in a recent study [ 69 ].…”